Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist Article Swipe

PDF

Susana Frago , Ryan Nicholls , Madeleine Strickland , Jennifer Hughes , Christopher Williams , Lee Garner , Mirvat Surakhy , Rory Maclean , Dellel Rezgui , Stuart Prince , Oliver Zaccheo , Daniel Ebner , Sabina Sanegre , Sheng Yu , Francesca M. Buffa , Matthew P. Crump , A. Bassim Hassan ·

YOU? · · 2016 · Open Access · · DOI: https://doi.org/10.1073/pnas.1513023113

Significance During 150 million years of mammalian evolution, the membrane-bound mannose 6-phosphate receptor evolved high-affinity binding loops for insulin-like growth factor 2. It remains unknown whether this highly evolved ligand interaction is optimal, and whether it can be further evolved. We addressed these questions using a mutation and selection strategy that incorporated surface display and protein structure. Multiple mutations of all the binding loops were identified and improved affinity by 100-fold when combined, yet retained IGF2 specificity. Structurally, IGF2 surface interactions with binding loops were reshaped, indicating that binding site evolution could not be predicted. High IGF2 affinity binding domains could selectively inhibit IGF2-dependent cell signaling, and may be applied in therapeutic IGF2 targeting in cancer.

Related Topics

Concepts

Insulin-like growth factor 2 receptor Plasma protein binding Biology Growth factor Mutation Cell biology Receptor Chemistry Biophysics Biochemistry Gene Insulin-like growth factor 1 receptor

Metadata

Type: article
Language: en
Landing Page: https://doi.org/10.1073/pnas.1513023113
PDF: https://www.pnas.org/content/pnas/113/20/E2766.full.pdf
OA Status: bronze
Cited By: 25
References: 59
Related Works: 10
OpenAlex ID: https://openalex.org/W2346928387

All OpenAlex metadata

Raw OpenAlex JSON

OpenAlex ID: https://openalex.org/W2346928387

Canonical identifier for this work in OpenAlex
DOI: https://doi.org/10.1073/pnas.1513023113

Digital Object Identifier
Title: Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist

Work title
Type: article

OpenAlex work type
Language: en

Primary language
Publication year: 2016

Year of publication
Publication date: 2016-05-02

Full publication date if available
Authors: Susana Frago, Ryan Nicholls, Madeleine Strickland, Jennifer Hughes, Christopher Williams, Lee Garner, Mirvat Surakhy, Rory Maclean, Dellel Rezgui, Stuart Prince, Oliver Zaccheo, Daniel Ebner, Sabina Sanegre, Sheng Yu, Francesca M. Buffa, Matthew P. Crump, A. Bassim Hassan

List of authors in order
Landing page: https://doi.org/10.1073/pnas.1513023113

Publisher landing page
PDF URL: https://www.pnas.org/content/pnas/113/20/E2766.full.pdf

Direct link to full text PDF
Open access: Yes

Whether a free full text is available
OA status: bronze

Open access status per OpenAlex
OA URL: https://www.pnas.org/content/pnas/113/20/E2766.full.pdf

Direct OA link when available
Concepts: Insulin-like growth factor 2 receptor, Plasma protein binding, Biology, Growth factor, Mutation, Cell biology, Receptor, Chemistry, Biophysics, Biochemistry, Gene, Insulin-like growth factor 1 receptor

Top concepts (fields/topics) attached by OpenAlex
Cited by: 25

Total citation count in OpenAlex
Citations by year (recent): 2025: 1, 2024: 3, 2023: 3, 2022: 1, 2021: 2

Per-year citation counts (last 5 years)
References (count): 59

Number of works referenced by this work
Related works (count): 10

Other works algorithmically related by OpenAlex

Full payload

id	https://openalex.org/W2346928387
doi	https://doi.org/10.1073/pnas.1513023113
ids.doi	https://doi.org/10.1073/pnas.1513023113
ids.mag	2346928387
ids.pmid	https://pubmed.ncbi.nlm.nih.gov/27140600
ids.openalex	https://openalex.org/W2346928387
fwci	2.52485599
mesh[0].qualifier_ui
mesh[0].descriptor_ui	D000328
mesh[0].is_major_topic	False
mesh[0].qualifier_name
mesh[0].descriptor_name	Adult
mesh[1].qualifier_ui
mesh[1].descriptor_ui	D000595
mesh[1].is_major_topic	False
mesh[1].qualifier_name
mesh[1].descriptor_name	Amino Acid Sequence
mesh[2].qualifier_ui
mesh[2].descriptor_ui	D019943
mesh[2].is_major_topic	False
mesh[2].qualifier_name
mesh[2].descriptor_name	Amino Acid Substitution
mesh[3].qualifier_ui
mesh[3].descriptor_ui	D045744
mesh[3].is_major_topic	False
mesh[3].qualifier_name
mesh[3].descriptor_name	Cell Line, Tumor
mesh[4].qualifier_ui
mesh[4].descriptor_ui	D018360
mesh[4].is_major_topic	False
mesh[4].qualifier_name
mesh[4].descriptor_name	Crystallography, X-Ray
mesh[5].qualifier_ui
mesh[5].descriptor_ui	D019020
mesh[5].is_major_topic	False
mesh[5].qualifier_name
mesh[5].descriptor_name	Directed Molecular Evolution
mesh[6].qualifier_ui
mesh[6].descriptor_ui	D006801
mesh[6].is_major_topic	False
mesh[6].qualifier_name
mesh[6].descriptor_name	Humans
mesh[7].qualifier_ui	Q000737
mesh[7].descriptor_ui	D007335
mesh[7].is_major_topic	False
mesh[7].qualifier_name	chemistry
mesh[7].descriptor_name	Insulin-Like Growth Factor II
mesh[8].qualifier_ui	Q000235
mesh[8].descriptor_ui	D007335
mesh[8].is_major_topic	False
mesh[8].qualifier_name	genetics
mesh[8].descriptor_name	Insulin-Like Growth Factor II
mesh[9].qualifier_ui	Q000378
mesh[9].descriptor_ui	D007335
mesh[9].is_major_topic	False
mesh[9].qualifier_name	metabolism
mesh[9].descriptor_name	Insulin-Like Growth Factor II
mesh[10].qualifier_ui
mesh[10].descriptor_ui	D008958
mesh[10].is_major_topic	False
mesh[10].qualifier_name
mesh[10].descriptor_name	Models, Molecular
mesh[11].qualifier_ui
mesh[11].descriptor_ui	D010843
mesh[11].is_major_topic	False
mesh[11].qualifier_name
mesh[11].descriptor_name	Pichia
mesh[12].qualifier_ui
mesh[12].descriptor_ui	D011485
mesh[12].is_major_topic	False
mesh[12].qualifier_name
mesh[12].descriptor_name	Protein Binding
mesh[13].qualifier_ui
mesh[13].descriptor_ui	D054730
mesh[13].is_major_topic	False
mesh[13].qualifier_name
mesh[13].descriptor_name	Protein Interaction Domains and Motifs
mesh[14].qualifier_ui	Q000037
mesh[14].descriptor_ui	D017527
mesh[14].is_major_topic	False
mesh[14].qualifier_name	antagonists & inhibitors
mesh[14].descriptor_name	Receptor, IGF Type 2
mesh[15].qualifier_ui	Q000737
mesh[15].descriptor_ui	D017527
mesh[15].is_major_topic	False
mesh[15].qualifier_name	chemistry
mesh[15].descriptor_name	Receptor, IGF Type 2
mesh[16].qualifier_ui	Q000235
mesh[16].descriptor_ui	D017527
mesh[16].is_major_topic	False
mesh[16].qualifier_name	genetics
mesh[16].descriptor_name	Receptor, IGF Type 2
mesh[17].qualifier_ui	Q000378
mesh[17].descriptor_ui	D017527
mesh[17].is_major_topic	False
mesh[17].qualifier_name	metabolism
mesh[17].descriptor_name	Receptor, IGF Type 2
mesh[18].qualifier_ui
mesh[18].descriptor_ui	D000328
mesh[18].is_major_topic	False
mesh[18].qualifier_name
mesh[18].descriptor_name	Adult
mesh[19].qualifier_ui
mesh[19].descriptor_ui	D000595
mesh[19].is_major_topic	False
mesh[19].qualifier_name
mesh[19].descriptor_name	Amino Acid Sequence
mesh[20].qualifier_ui
mesh[20].descriptor_ui	D019943
mesh[20].is_major_topic	False
mesh[20].qualifier_name
mesh[20].descriptor_name	Amino Acid Substitution
mesh[21].qualifier_ui
mesh[21].descriptor_ui	D045744
mesh[21].is_major_topic	False
mesh[21].qualifier_name
mesh[21].descriptor_name	Cell Line, Tumor
mesh[22].qualifier_ui
mesh[22].descriptor_ui	D018360
mesh[22].is_major_topic	False
mesh[22].qualifier_name
mesh[22].descriptor_name	Crystallography, X-Ray
mesh[23].qualifier_ui
mesh[23].descriptor_ui	D019020
mesh[23].is_major_topic	False
mesh[23].qualifier_name
mesh[23].descriptor_name	Directed Molecular Evolution
mesh[24].qualifier_ui
mesh[24].descriptor_ui	D006801
mesh[24].is_major_topic	False
mesh[24].qualifier_name
mesh[24].descriptor_name	Humans
mesh[25].qualifier_ui	Q000737
mesh[25].descriptor_ui	D007335
mesh[25].is_major_topic	False
mesh[25].qualifier_name	chemistry
mesh[25].descriptor_name	Insulin-Like Growth Factor II
mesh[26].qualifier_ui	Q000235
mesh[26].descriptor_ui	D007335
mesh[26].is_major_topic	False
mesh[26].qualifier_name	genetics
mesh[26].descriptor_name	Insulin-Like Growth Factor II
mesh[27].qualifier_ui	Q000378
mesh[27].descriptor_ui	D007335
mesh[27].is_major_topic	False
mesh[27].qualifier_name	metabolism
mesh[27].descriptor_name	Insulin-Like Growth Factor II
mesh[28].qualifier_ui
mesh[28].descriptor_ui	D008958
mesh[28].is_major_topic	False
mesh[28].qualifier_name
mesh[28].descriptor_name	Models, Molecular
mesh[29].qualifier_ui
mesh[29].descriptor_ui	D010843
mesh[29].is_major_topic	False
mesh[29].qualifier_name
mesh[29].descriptor_name	Pichia
mesh[30].qualifier_ui
mesh[30].descriptor_ui	D011485
mesh[30].is_major_topic	False
mesh[30].qualifier_name
mesh[30].descriptor_name	Protein Binding
mesh[31].qualifier_ui
mesh[31].descriptor_ui	D054730
mesh[31].is_major_topic	False
mesh[31].qualifier_name
mesh[31].descriptor_name	Protein Interaction Domains and Motifs
mesh[32].qualifier_ui	Q000037
mesh[32].descriptor_ui	D017527
mesh[32].is_major_topic	False
mesh[32].qualifier_name	antagonists & inhibitors
mesh[32].descriptor_name	Receptor, IGF Type 2
mesh[33].qualifier_ui	Q000737
mesh[33].descriptor_ui	D017527
mesh[33].is_major_topic	False
mesh[33].qualifier_name	chemistry
mesh[33].descriptor_name	Receptor, IGF Type 2
mesh[34].qualifier_ui	Q000235
mesh[34].descriptor_ui	D017527
mesh[34].is_major_topic	False
mesh[34].qualifier_name	genetics
mesh[34].descriptor_name	Receptor, IGF Type 2
mesh[35].qualifier_ui	Q000378
mesh[35].descriptor_ui	D017527
mesh[35].is_major_topic	False
mesh[35].qualifier_name	metabolism
mesh[35].descriptor_name	Receptor, IGF Type 2
mesh[36].qualifier_ui
mesh[36].descriptor_ui	D000328
mesh[36].is_major_topic	False
mesh[36].qualifier_name
mesh[36].descriptor_name	Adult
mesh[37].qualifier_ui
mesh[37].descriptor_ui	D000595
mesh[37].is_major_topic	False
mesh[37].qualifier_name
mesh[37].descriptor_name	Amino Acid Sequence
mesh[38].qualifier_ui
mesh[38].descriptor_ui	D019943
mesh[38].is_major_topic	False
mesh[38].qualifier_name
mesh[38].descriptor_name	Amino Acid Substitution
mesh[39].qualifier_ui
mesh[39].descriptor_ui	D045744
mesh[39].is_major_topic	False
mesh[39].qualifier_name
mesh[39].descriptor_name	Cell Line, Tumor
mesh[40].qualifier_ui
mesh[40].descriptor_ui	D018360
mesh[40].is_major_topic	False
mesh[40].qualifier_name
mesh[40].descriptor_name	Crystallography, X-Ray
mesh[41].qualifier_ui
mesh[41].descriptor_ui	D019020
mesh[41].is_major_topic	False
mesh[41].qualifier_name
mesh[41].descriptor_name	Directed Molecular Evolution
mesh[42].qualifier_ui
mesh[42].descriptor_ui	D006801
mesh[42].is_major_topic	False
mesh[42].qualifier_name
mesh[42].descriptor_name	Humans
mesh[43].qualifier_ui	Q000737
mesh[43].descriptor_ui	D007335
mesh[43].is_major_topic	False
mesh[43].qualifier_name	chemistry
mesh[43].descriptor_name	Insulin-Like Growth Factor II
mesh[44].qualifier_ui	Q000235
mesh[44].descriptor_ui	D007335
mesh[44].is_major_topic	False
mesh[44].qualifier_name	genetics
mesh[44].descriptor_name	Insulin-Like Growth Factor II
mesh[45].qualifier_ui	Q000378
mesh[45].descriptor_ui	D007335
mesh[45].is_major_topic	False
mesh[45].qualifier_name	metabolism
mesh[45].descriptor_name	Insulin-Like Growth Factor II
mesh[46].qualifier_ui
mesh[46].descriptor_ui	D008958
mesh[46].is_major_topic	False
mesh[46].qualifier_name
mesh[46].descriptor_name	Models, Molecular
mesh[47].qualifier_ui
mesh[47].descriptor_ui	D010843
mesh[47].is_major_topic	False
mesh[47].qualifier_name
mesh[47].descriptor_name	Pichia
mesh[48].qualifier_ui
mesh[48].descriptor_ui	D011485
mesh[48].is_major_topic	False
mesh[48].qualifier_name
mesh[48].descriptor_name	Protein Binding
mesh[49].qualifier_ui
mesh[49].descriptor_ui	D054730
mesh[49].is_major_topic	False
mesh[49].qualifier_name
mesh[49].descriptor_name	Protein Interaction Domains and Motifs
type	article
title	Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist
awards[0].id	https://openalex.org/G875923395
awards[0].funder_id	https://openalex.org/F4320307874
awards[0].display_name
awards[0].funder_award_id	NK
awards[0].funder_display_name	Wellcome
awards[1].id	https://openalex.org/G1333340707
awards[1].funder_id	https://openalex.org/F4320334626
awards[1].display_name
awards[1].funder_award_id	MC_PC_15029
awards[1].funder_display_name	Medical Research Council
awards[2].id	https://openalex.org/G7681971961
awards[2].funder_id	https://openalex.org/F4320319985
awards[2].display_name
awards[2].funder_award_id	C429
awards[2].funder_display_name	Cancer Research UK
awards[3].id	https://openalex.org/G6626272035
awards[3].funder_id	https://openalex.org/F4320319990
awards[3].display_name
awards[3].funder_award_id	BRU
awards[3].funder_display_name	National Institute for Health and Care Research
biblio.issue	20
biblio.volume	113
biblio.last_page	75
biblio.first_page	E2766
topics[0].id	https://openalex.org/T10748
topics[0].field.id	https://openalex.org/fields/27
topics[0].field.display_name	Medicine
topics[0].score	0.9991999864578247
topics[0].domain.id	https://openalex.org/domains/4
topics[0].domain.display_name	Health Sciences
topics[0].subfield.id	https://openalex.org/subfields/2712
topics[0].subfield.display_name	Endocrinology, Diabetes and Metabolism
topics[0].display_name	Growth Hormone and Insulin-like Growth Factors
topics[1].id	https://openalex.org/T10602
topics[1].field.id	https://openalex.org/fields/13
topics[1].field.display_name	Biochemistry, Genetics and Molecular Biology
topics[1].score	0.9947999715805054
topics[1].domain.id	https://openalex.org/domains/1
topics[1].domain.display_name	Life Sciences
topics[1].subfield.id	https://openalex.org/subfields/1312
topics[1].subfield.display_name	Molecular Biology
topics[1].display_name	Glycosylation and Glycoproteins Research
topics[2].id	https://openalex.org/T11157
topics[2].field.id	https://openalex.org/fields/27
topics[2].field.display_name	Medicine
topics[2].score	0.9914000034332275
topics[2].domain.id	https://openalex.org/domains/4
topics[2].domain.display_name	Health Sciences
topics[2].subfield.id	https://openalex.org/subfields/2716
topics[2].subfield.display_name	Genetics
topics[2].display_name	Chronic Lymphocytic Leukemia Research
funders[0].id	https://openalex.org/F4320307874
funders[0].ror	https://ror.org/029chgv08
funders[0].display_name	Wellcome
funders[1].id	https://openalex.org/F4320319985
funders[1].ror	https://ror.org/054225q67
funders[1].display_name	Cancer Research UK
funders[2].id	https://openalex.org/F4320319990
funders[2].ror	https://ror.org/0187kwz08
funders[2].display_name	National Institute for Health and Care Research
funders[3].id	https://openalex.org/F4320334626
funders[3].ror	https://ror.org/03x94j517
funders[3].display_name	Medical Research Council
is_xpac	False
apc_list
apc_paid
concepts[0].id	https://openalex.org/C21936154
concepts[0].level	5
concepts[0].score	0.6108817458152771
concepts[0].wikidata	https://www.wikidata.org/wiki/Q14911786
concepts[0].display_name	Insulin-like growth factor 2 receptor
concepts[1].id	https://openalex.org/C51639874
concepts[1].level	2
concepts[1].score	0.4444507956504822
concepts[1].wikidata	https://www.wikidata.org/wiki/Q167149
concepts[1].display_name	Plasma protein binding
concepts[2].id	https://openalex.org/C86803240
concepts[2].level	0
concepts[2].score	0.4366511404514313
concepts[2].wikidata	https://www.wikidata.org/wiki/Q420
concepts[2].display_name	Biology
concepts[3].id	https://openalex.org/C2775960820
concepts[3].level	3
concepts[3].score	0.42110076546669006
concepts[3].wikidata	https://www.wikidata.org/wiki/Q408378
concepts[3].display_name	Growth factor
concepts[4].id	https://openalex.org/C501734568
concepts[4].level	3
concepts[4].score	0.4208657145500183
concepts[4].wikidata	https://www.wikidata.org/wiki/Q42918
concepts[4].display_name	Mutation
concepts[5].id	https://openalex.org/C95444343
concepts[5].level	1
concepts[5].score	0.40815281867980957
concepts[5].wikidata	https://www.wikidata.org/wiki/Q7141
concepts[5].display_name	Cell biology
concepts[6].id	https://openalex.org/C170493617
concepts[6].level	2
concepts[6].score	0.38280412554740906
concepts[6].wikidata	https://www.wikidata.org/wiki/Q208467
concepts[6].display_name	Receptor
concepts[7].id	https://openalex.org/C185592680
concepts[7].level	0
concepts[7].score	0.36658111214637756
concepts[7].wikidata	https://www.wikidata.org/wiki/Q2329
concepts[7].display_name	Chemistry
concepts[8].id	https://openalex.org/C12554922
concepts[8].level	1
concepts[8].score	0.342837929725647
concepts[8].wikidata	https://www.wikidata.org/wiki/Q7100
concepts[8].display_name	Biophysics
concepts[9].id	https://openalex.org/C55493867
concepts[9].level	1
concepts[9].score	0.2802128791809082
concepts[9].wikidata	https://www.wikidata.org/wiki/Q7094
concepts[9].display_name	Biochemistry
concepts[10].id	https://openalex.org/C104317684
concepts[10].level	2
concepts[10].score	0.2093629539012909
concepts[10].wikidata	https://www.wikidata.org/wiki/Q7187
concepts[10].display_name	Gene
concepts[11].id	https://openalex.org/C144174609
concepts[11].level	4
concepts[11].score	0.10632273554801941
concepts[11].wikidata	https://www.wikidata.org/wiki/Q14901457
concepts[11].display_name	Insulin-like growth factor 1 receptor
keywords[0].id	https://openalex.org/keywords/insulin-like-growth-factor-2-receptor
keywords[0].score	0.6108817458152771
keywords[0].display_name	Insulin-like growth factor 2 receptor
keywords[1].id	https://openalex.org/keywords/plasma-protein-binding
keywords[1].score	0.4444507956504822
keywords[1].display_name	Plasma protein binding
keywords[2].id	https://openalex.org/keywords/biology
keywords[2].score	0.4366511404514313
keywords[2].display_name	Biology
keywords[3].id	https://openalex.org/keywords/growth-factor
keywords[3].score	0.42110076546669006
keywords[3].display_name	Growth factor
keywords[4].id	https://openalex.org/keywords/mutation
keywords[4].score	0.4208657145500183
keywords[4].display_name	Mutation
keywords[5].id	https://openalex.org/keywords/cell-biology
keywords[5].score	0.40815281867980957
keywords[5].display_name	Cell biology
keywords[6].id	https://openalex.org/keywords/receptor
keywords[6].score	0.38280412554740906
keywords[6].display_name	Receptor
keywords[7].id	https://openalex.org/keywords/chemistry
keywords[7].score	0.36658111214637756
keywords[7].display_name	Chemistry
keywords[8].id	https://openalex.org/keywords/biophysics
keywords[8].score	0.342837929725647
keywords[8].display_name	Biophysics
keywords[9].id	https://openalex.org/keywords/biochemistry
keywords[9].score	0.2802128791809082
keywords[9].display_name	Biochemistry
keywords[10].id	https://openalex.org/keywords/gene
keywords[10].score	0.2093629539012909
keywords[10].display_name	Gene
keywords[11].id	https://openalex.org/keywords/insulin-like-growth-factor-1-receptor
keywords[11].score	0.10632273554801941
keywords[11].display_name	Insulin-like growth factor 1 receptor
language	en
locations[0].id	doi:10.1073/pnas.1513023113
locations[0].is_oa	True
locations[0].source.id	https://openalex.org/S125754415
locations[0].source.issn	0027-8424, 1091-6490
locations[0].source.type	journal
locations[0].source.is_oa	False
locations[0].source.issn_l	0027-8424
locations[0].source.is_core	True
locations[0].source.is_in_doaj	False
locations[0].source.display_name	Proceedings of the National Academy of Sciences
locations[0].source.host_organization	https://openalex.org/P4310320052
locations[0].source.host_organization_name	National Academy of Sciences
locations[0].source.host_organization_lineage	https://openalex.org/P4310320052
locations[0].source.host_organization_lineage_names	National Academy of Sciences
locations[0].license
locations[0].pdf_url	https://www.pnas.org/content/pnas/113/20/E2766.full.pdf
locations[0].version	publishedVersion
locations[0].raw_type	journal-article
locations[0].license_id
locations[0].is_accepted	True
locations[0].is_published	True
locations[0].raw_source_name	Proceedings of the National Academy of Sciences
locations[0].landing_page_url	https://doi.org/10.1073/pnas.1513023113
locations[1].id	pmid:27140600
locations[1].is_oa	False
locations[1].source.id	https://openalex.org/S4306525036
locations[1].source.issn
locations[1].source.type	repository
locations[1].source.is_oa	False
locations[1].source.issn_l
locations[1].source.is_core	False
locations[1].source.is_in_doaj	False
locations[1].source.display_name	PubMed
locations[1].source.host_organization	https://openalex.org/I1299303238
locations[1].source.host_organization_name	National Institutes of Health
locations[1].source.host_organization_lineage	https://openalex.org/I1299303238
locations[1].license
locations[1].pdf_url
locations[1].version	publishedVersion
locations[1].raw_type
locations[1].license_id
locations[1].is_accepted	True
locations[1].is_published	True
locations[1].raw_source_name	Proceedings of the National Academy of Sciences of the United States of America
locations[1].landing_page_url	https://pubmed.ncbi.nlm.nih.gov/27140600
locations[2].id	pmh:oai:research-information.bris.ac.uk:openaire_cris_publications/898008f4-a688-4638-9aca-222cac15ff7d
locations[2].is_oa	True
locations[2].source.id	https://openalex.org/S4306400895
locations[2].source.issn
locations[2].source.type	repository
locations[2].source.is_oa	False
locations[2].source.issn_l
locations[2].source.is_core	False
locations[2].source.is_in_doaj	False
locations[2].source.display_name	Bristol Research (University of Bristol)
locations[2].source.host_organization	https://openalex.org/I36234482
locations[2].source.host_organization_name	University of Bristol
locations[2].source.host_organization_lineage	https://openalex.org/I36234482
locations[2].license	other-oa
locations[2].pdf_url
locations[2].version	publishedVersion
locations[2].raw_type	info:eu-repo/semantics/publishedVersion
locations[2].license_id	https://openalex.org/licenses/other-oa
locations[2].is_accepted	True
locations[2].is_published	True
locations[2].raw_source_name	Frago, S, Nicholls, R, Strickland, M, Hughes, J, Williams, C, Garner, L, Surakhy, M, Maclean, R, Rezgui, D A R, Prince, S, Zaccheo, O, Ebner, D, Sanegre, S, Yu, S, Buffa, F M, Crump, M & Hassan, A B 2016, 'Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 20, pp. E2766-E2775. https://doi.org/10.1073/pnas.1513023113
locations[2].landing_page_url	https://research-information.bris.ac.uk/en/publications/898008f4-a688-4638-9aca-222cac15ff7d
locations[3].id	pmh:oai:europepmc.org:4045659
locations[3].is_oa	False
locations[3].source.id	https://openalex.org/S4306400806
locations[3].source.issn
locations[3].source.type	repository
locations[3].source.is_oa	False
locations[3].source.issn_l
locations[3].source.is_core	False
locations[3].source.is_in_doaj	False
locations[3].source.display_name	Europe PMC (PubMed Central)
locations[3].source.host_organization	https://openalex.org/I1303153112
locations[3].source.host_organization_name	European Bioinformatics Institute
locations[3].source.host_organization_lineage	https://openalex.org/I1303153112
locations[3].license
locations[3].pdf_url
locations[3].version	submittedVersion
locations[3].raw_type	Text
locations[3].license_id
locations[3].is_accepted	False
locations[3].is_published	False
locations[3].raw_source_name
locations[3].landing_page_url	https://www.ncbi.nlm.nih.gov/pmc/articles/4878476
locations[4].id	pmh:oai:pubmedcentral.nih.gov:4878476
locations[4].is_oa	True
locations[4].source.id	https://openalex.org/S2764455111
locations[4].source.issn
locations[4].source.type	repository
locations[4].source.is_oa	False
locations[4].source.issn_l
locations[4].source.is_core	False
locations[4].source.is_in_doaj	False
locations[4].source.display_name	PubMed Central
locations[4].source.host_organization	https://openalex.org/I1299303238
locations[4].source.host_organization_name	National Institutes of Health
locations[4].source.host_organization_lineage	https://openalex.org/I1299303238
locations[4].license
locations[4].pdf_url
locations[4].version	submittedVersion
locations[4].raw_type	Text
locations[4].license_id
locations[4].is_accepted	False
locations[4].is_published	False
locations[4].raw_source_name
locations[4].landing_page_url	http://doi.org/10.1073/pnas.1513023113
locations[5].id	pmh:oai:research-information.bris.ac.uk:publications/898008f4-a688-4638-9aca-222cac15ff7d
locations[5].is_oa	False
locations[5].source.id	https://openalex.org/S4306400895
locations[5].source.issn
locations[5].source.type	repository
locations[5].source.is_oa	False
locations[5].source.issn_l
locations[5].source.is_core	False
locations[5].source.is_in_doaj	False
locations[5].source.display_name	Bristol Research (University of Bristol)
locations[5].source.host_organization	https://openalex.org/I36234482
locations[5].source.host_organization_name	University of Bristol
locations[5].source.host_organization_lineage	https://openalex.org/I36234482
locations[5].license
locations[5].pdf_url
locations[5].version	submittedVersion
locations[5].raw_type
locations[5].license_id
locations[5].is_accepted	False
locations[5].is_published	False
locations[5].raw_source_name
locations[5].landing_page_url	https://hdl.handle.net/1983/898008f4-a688-4638-9aca-222cac15ff7d
indexed_in	crossref, pubmed
authorships[0].author.id	https://openalex.org/A5023025738
authorships[0].author.orcid	https://orcid.org/0000-0002-1369-1328
authorships[0].author.display_name	Susana Frago
authorships[0].countries	GB
authorships[0].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[0].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[0].institutions[0].id	https://openalex.org/I40120149
authorships[0].institutions[0].ror	https://ror.org/052gg0110
authorships[0].institutions[0].type	education
authorships[0].institutions[0].lineage	https://openalex.org/I40120149
authorships[0].institutions[0].country_code	GB
authorships[0].institutions[0].display_name	University of Oxford
authorships[0].author_position	first
authorships[0].raw_author_name	Susana Frago
authorships[0].is_corresponding	False
authorships[0].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[1].author.id	https://openalex.org/A5023218765
authorships[1].author.orcid
authorships[1].author.display_name	Ryan Nicholls
authorships[1].countries	GB
authorships[1].affiliations[0].institution_ids	https://openalex.org/I36234482
authorships[1].affiliations[0].raw_affiliation_string	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[1].institutions[0].id	https://openalex.org/I36234482
authorships[1].institutions[0].ror	https://ror.org/0524sp257
authorships[1].institutions[0].type	education
authorships[1].institutions[0].lineage	https://openalex.org/I36234482
authorships[1].institutions[0].country_code	GB
authorships[1].institutions[0].display_name	University of Bristol
authorships[1].author_position	middle
authorships[1].raw_author_name	Ryan D. Nicholls
authorships[1].is_corresponding	False
authorships[1].raw_affiliation_strings	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[2].author.id	https://openalex.org/A5004110744
authorships[2].author.orcid	https://orcid.org/0000-0001-8160-070X
authorships[2].author.display_name	Madeleine Strickland
authorships[2].countries	GB
authorships[2].affiliations[0].institution_ids	https://openalex.org/I36234482
authorships[2].affiliations[0].raw_affiliation_string	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[2].institutions[0].id	https://openalex.org/I36234482
authorships[2].institutions[0].ror	https://ror.org/0524sp257
authorships[2].institutions[0].type	education
authorships[2].institutions[0].lineage	https://openalex.org/I36234482
authorships[2].institutions[0].country_code	GB
authorships[2].institutions[0].display_name	University of Bristol
authorships[2].author_position	middle
authorships[2].raw_author_name	Madeleine Strickland
authorships[2].is_corresponding	False
authorships[2].raw_affiliation_strings	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[3].author.id	https://openalex.org/A5102148846
authorships[3].author.orcid
authorships[3].author.display_name	Jennifer Hughes
authorships[3].countries	GB
authorships[3].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[3].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[3].institutions[0].id	https://openalex.org/I40120149
authorships[3].institutions[0].ror	https://ror.org/052gg0110
authorships[3].institutions[0].type	education
authorships[3].institutions[0].lineage	https://openalex.org/I40120149
authorships[3].institutions[0].country_code	GB
authorships[3].institutions[0].display_name	University of Oxford
authorships[3].author_position	middle
authorships[3].raw_author_name	Jennifer Hughes
authorships[3].is_corresponding	False
authorships[3].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[4].author.id	https://openalex.org/A5056074050
authorships[4].author.orcid	https://orcid.org/0000-0001-5806-9842
authorships[4].author.display_name	Christopher Williams
authorships[4].countries	GB
authorships[4].affiliations[0].institution_ids	https://openalex.org/I36234482
authorships[4].affiliations[0].raw_affiliation_string	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[4].institutions[0].id	https://openalex.org/I36234482
authorships[4].institutions[0].ror	https://ror.org/0524sp257
authorships[4].institutions[0].type	education
authorships[4].institutions[0].lineage	https://openalex.org/I36234482
authorships[4].institutions[0].country_code	GB
authorships[4].institutions[0].display_name	University of Bristol
authorships[4].author_position	middle
authorships[4].raw_author_name	Christopher Williams
authorships[4].is_corresponding	False
authorships[4].raw_affiliation_strings	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[5].author.id	https://openalex.org/A5058534621
authorships[5].author.orcid	https://orcid.org/0000-0003-3799-0266
authorships[5].author.display_name	Lee Garner
authorships[5].countries	GB
authorships[5].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[5].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[5].institutions[0].id	https://openalex.org/I40120149
authorships[5].institutions[0].ror	https://ror.org/052gg0110
authorships[5].institutions[0].type	education
authorships[5].institutions[0].lineage	https://openalex.org/I40120149
authorships[5].institutions[0].country_code	GB
authorships[5].institutions[0].display_name	University of Oxford
authorships[5].author_position	middle
authorships[5].raw_author_name	Lee Garner
authorships[5].is_corresponding	False
authorships[5].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[6].author.id	https://openalex.org/A5044964326
authorships[6].author.orcid	https://orcid.org/0000-0001-7101-984X
authorships[6].author.display_name	Mirvat Surakhy
authorships[6].countries	GB
authorships[6].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[6].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[6].institutions[0].id	https://openalex.org/I40120149
authorships[6].institutions[0].ror	https://ror.org/052gg0110
authorships[6].institutions[0].type	education
authorships[6].institutions[0].lineage	https://openalex.org/I40120149
authorships[6].institutions[0].country_code	GB
authorships[6].institutions[0].display_name	University of Oxford
authorships[6].author_position	middle
authorships[6].raw_author_name	Mirvat Surakhy
authorships[6].is_corresponding	False
authorships[6].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[7].author.id	https://openalex.org/A5010535866
authorships[7].author.orcid	https://orcid.org/0000-0002-9686-0501
authorships[7].author.display_name	Rory Maclean
authorships[7].countries	GB
authorships[7].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[7].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[7].institutions[0].id	https://openalex.org/I40120149
authorships[7].institutions[0].ror	https://ror.org/052gg0110
authorships[7].institutions[0].type	education
authorships[7].institutions[0].lineage	https://openalex.org/I40120149
authorships[7].institutions[0].country_code	GB
authorships[7].institutions[0].display_name	University of Oxford
authorships[7].author_position	middle
authorships[7].raw_author_name	Rory Maclean
authorships[7].is_corresponding	False
authorships[7].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[8].author.id	https://openalex.org/A5057032048
authorships[8].author.orcid
authorships[8].author.display_name	Dellel Rezgui
authorships[8].countries	GB
authorships[8].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[8].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[8].institutions[0].id	https://openalex.org/I40120149
authorships[8].institutions[0].ror	https://ror.org/052gg0110
authorships[8].institutions[0].type	education
authorships[8].institutions[0].lineage	https://openalex.org/I40120149
authorships[8].institutions[0].country_code	GB
authorships[8].institutions[0].display_name	University of Oxford
authorships[8].author_position	middle
authorships[8].raw_author_name	Dellel Rezgui
authorships[8].is_corresponding	False
authorships[8].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[9].author.id	https://openalex.org/A5112470760
authorships[9].author.orcid	https://orcid.org/0009-0007-4916-5876
authorships[9].author.display_name	Stuart Prince
authorships[9].countries	GB
authorships[9].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[9].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[9].institutions[0].id	https://openalex.org/I40120149
authorships[9].institutions[0].ror	https://ror.org/052gg0110
authorships[9].institutions[0].type	education
authorships[9].institutions[0].lineage	https://openalex.org/I40120149
authorships[9].institutions[0].country_code	GB
authorships[9].institutions[0].display_name	University of Oxford
authorships[9].author_position	middle
authorships[9].raw_author_name	Stuart N. Prince
authorships[9].is_corresponding	False
authorships[9].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[10].author.id	https://openalex.org/A5062811221
authorships[10].author.orcid
authorships[10].author.display_name	Oliver Zaccheo
authorships[10].countries	GB
authorships[10].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[10].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[10].institutions[0].id	https://openalex.org/I40120149
authorships[10].institutions[0].ror	https://ror.org/052gg0110
authorships[10].institutions[0].type	education
authorships[10].institutions[0].lineage	https://openalex.org/I40120149
authorships[10].institutions[0].country_code	GB
authorships[10].institutions[0].display_name	University of Oxford
authorships[10].author_position	middle
authorships[10].raw_author_name	Oliver J. Zaccheo
authorships[10].is_corresponding	False
authorships[10].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[11].author.id	https://openalex.org/A5091138255
authorships[11].author.orcid	https://orcid.org/0000-0002-6495-7026
authorships[11].author.display_name	Daniel Ebner
authorships[11].countries	GB
authorships[11].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[11].affiliations[0].raw_affiliation_string	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom;
authorships[11].institutions[0].id	https://openalex.org/I40120149
authorships[11].institutions[0].ror	https://ror.org/052gg0110
authorships[11].institutions[0].type	education
authorships[11].institutions[0].lineage	https://openalex.org/I40120149
authorships[11].institutions[0].country_code	GB
authorships[11].institutions[0].display_name	University of Oxford
authorships[11].author_position	middle
authorships[11].raw_author_name	Daniel Ebner
authorships[11].is_corresponding	False
authorships[11].raw_affiliation_strings	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom;
authorships[12].author.id	https://openalex.org/A5019904512
authorships[12].author.orcid	https://orcid.org/0000-0003-0271-478X
authorships[12].author.display_name	Sabina Sanegre
authorships[12].countries	GB
authorships[12].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[12].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[12].institutions[0].id	https://openalex.org/I40120149
authorships[12].institutions[0].ror	https://ror.org/052gg0110
authorships[12].institutions[0].type	education
authorships[12].institutions[0].lineage	https://openalex.org/I40120149
authorships[12].institutions[0].country_code	GB
authorships[12].institutions[0].display_name	University of Oxford
authorships[12].author_position	middle
authorships[12].raw_author_name	Sabina Sanegre
authorships[12].is_corresponding	False
authorships[12].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[13].author.id	https://openalex.org/A5111580905
authorships[13].author.orcid
authorships[13].author.display_name	Sheng Yu
authorships[13].countries	GB
authorships[13].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[13].affiliations[0].raw_affiliation_string	Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
authorships[13].institutions[0].id	https://openalex.org/I40120149
authorships[13].institutions[0].ror	https://ror.org/052gg0110
authorships[13].institutions[0].type	education
authorships[13].institutions[0].lineage	https://openalex.org/I40120149
authorships[13].institutions[0].country_code	GB
authorships[13].institutions[0].display_name	University of Oxford
authorships[13].author_position	middle
authorships[13].raw_author_name	Sheng Yu
authorships[13].is_corresponding	False
authorships[13].raw_affiliation_strings	Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
authorships[14].author.id	https://openalex.org/A5075865182
authorships[14].author.orcid	https://orcid.org/0000-0003-0409-406X
authorships[14].author.display_name	Francesca M. Buffa
authorships[14].countries	GB
authorships[14].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[14].affiliations[0].raw_affiliation_string	Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
authorships[14].institutions[0].id	https://openalex.org/I40120149
authorships[14].institutions[0].ror	https://ror.org/052gg0110
authorships[14].institutions[0].type	education
authorships[14].institutions[0].lineage	https://openalex.org/I40120149
authorships[14].institutions[0].country_code	GB
authorships[14].institutions[0].display_name	University of Oxford
authorships[14].author_position	middle
authorships[14].raw_author_name	Francesca M. Buffa
authorships[14].is_corresponding	False
authorships[14].raw_affiliation_strings	Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
authorships[15].author.id	https://openalex.org/A5057320292
authorships[15].author.orcid	https://orcid.org/0000-0002-7868-5818
authorships[15].author.display_name	Matthew P. Crump
authorships[15].countries	GB
authorships[15].affiliations[0].institution_ids	https://openalex.org/I36234482
authorships[15].affiliations[0].raw_affiliation_string	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[15].institutions[0].id	https://openalex.org/I36234482
authorships[15].institutions[0].ror	https://ror.org/0524sp257
authorships[15].institutions[0].type	education
authorships[15].institutions[0].lineage	https://openalex.org/I36234482
authorships[15].institutions[0].country_code	GB
authorships[15].institutions[0].display_name	University of Bristol
authorships[15].author_position	middle
authorships[15].raw_author_name	Matthew P. Crump
authorships[15].is_corresponding	False
authorships[15].raw_affiliation_strings	Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom;
authorships[16].author.id	https://openalex.org/A5040594896
authorships[16].author.orcid	https://orcid.org/0000-0002-2517-6681
authorships[16].author.display_name	A. Bassim Hassan
authorships[16].countries	GB
authorships[16].affiliations[0].institution_ids	https://openalex.org/I40120149
authorships[16].affiliations[0].raw_affiliation_string	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authorships[16].institutions[0].id	https://openalex.org/I40120149
authorships[16].institutions[0].ror	https://ror.org/052gg0110
authorships[16].institutions[0].type	education
authorships[16].institutions[0].lineage	https://openalex.org/I40120149
authorships[16].institutions[0].country_code	GB
authorships[16].institutions[0].display_name	University of Oxford
authorships[16].author_position	last
authorships[16].raw_author_name	Andrew Bassim Hassan
authorships[16].is_corresponding	False
authorships[16].raw_affiliation_strings	Tumour Growth Control Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
has_content.pdf	True
has_content.grobid_xml	True
is_paratext	False
open_access.is_oa	True
open_access.oa_url	https://www.pnas.org/content/pnas/113/20/E2766.full.pdf
open_access.oa_status	bronze
open_access.any_repository_has_fulltext	False
created_date	2025-10-10T00:00:00
display_name	Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist
has_fulltext	True
is_retracted	False
updated_date	2025-11-06T03:46:38.306776
primary_topic.id	https://openalex.org/T10748
primary_topic.field.id	https://openalex.org/fields/27
primary_topic.field.display_name	Medicine
primary_topic.score	0.9991999864578247
primary_topic.domain.id	https://openalex.org/domains/4
primary_topic.domain.display_name	Health Sciences
primary_topic.subfield.id	https://openalex.org/subfields/2712
primary_topic.subfield.display_name	Endocrinology, Diabetes and Metabolism
primary_topic.display_name	Growth Hormone and Insulin-like Growth Factors
related_works	https://openalex.org/W1995184255, https://openalex.org/W4388301427, https://openalex.org/W2110783708, https://openalex.org/W2067487275, https://openalex.org/W2046453156, https://openalex.org/W1997064773, https://openalex.org/W2028048360, https://openalex.org/W1722688286, https://openalex.org/W2516192421, https://openalex.org/W2023358438
cited_by_count	25
counts_by_year[0].year	2025
counts_by_year[0].cited_by_count	1
counts_by_year[1].year	2024
counts_by_year[1].cited_by_count	3
counts_by_year[2].year	2023
counts_by_year[2].cited_by_count	3
counts_by_year[3].year	2022
counts_by_year[3].cited_by_count	1
counts_by_year[4].year	2021
counts_by_year[4].cited_by_count	2
counts_by_year[5].year	2020
counts_by_year[5].cited_by_count	5
counts_by_year[6].year	2019
counts_by_year[6].cited_by_count	2
counts_by_year[7].year	2018
counts_by_year[7].cited_by_count	1
counts_by_year[8].year	2017
counts_by_year[8].cited_by_count	4
counts_by_year[9].year	2016
counts_by_year[9].cited_by_count	3
locations_count	6
best_oa_location.id	doi:10.1073/pnas.1513023113
best_oa_location.is_oa	True
best_oa_location.source.id	https://openalex.org/S125754415
best_oa_location.source.issn	0027-8424, 1091-6490
best_oa_location.source.type	journal
best_oa_location.source.is_oa	False
best_oa_location.source.issn_l	0027-8424
best_oa_location.source.is_core	True
best_oa_location.source.is_in_doaj	False
best_oa_location.source.display_name	Proceedings of the National Academy of Sciences
best_oa_location.source.host_organization	https://openalex.org/P4310320052
best_oa_location.source.host_organization_name	National Academy of Sciences
best_oa_location.source.host_organization_lineage	https://openalex.org/P4310320052
best_oa_location.source.host_organization_lineage_names	National Academy of Sciences
best_oa_location.license
best_oa_location.pdf_url	https://www.pnas.org/content/pnas/113/20/E2766.full.pdf
best_oa_location.version	publishedVersion
best_oa_location.raw_type	journal-article
best_oa_location.license_id
best_oa_location.is_accepted	True
best_oa_location.is_published	True
best_oa_location.raw_source_name	Proceedings of the National Academy of Sciences
best_oa_location.landing_page_url	https://doi.org/10.1073/pnas.1513023113
primary_location.id	doi:10.1073/pnas.1513023113
primary_location.is_oa	True
primary_location.source.id	https://openalex.org/S125754415
primary_location.source.issn	0027-8424, 1091-6490
primary_location.source.type	journal
primary_location.source.is_oa	False
primary_location.source.issn_l	0027-8424
primary_location.source.is_core	True
primary_location.source.is_in_doaj	False
primary_location.source.display_name	Proceedings of the National Academy of Sciences
primary_location.source.host_organization	https://openalex.org/P4310320052
primary_location.source.host_organization_name	National Academy of Sciences
primary_location.source.host_organization_lineage	https://openalex.org/P4310320052
primary_location.source.host_organization_lineage_names	National Academy of Sciences
primary_location.license
primary_location.pdf_url	https://www.pnas.org/content/pnas/113/20/E2766.full.pdf
primary_location.version	publishedVersion
primary_location.raw_type	journal-article
primary_location.license_id
primary_location.is_accepted	True
primary_location.is_published	True
primary_location.raw_source_name	Proceedings of the National Academy of Sciences
primary_location.landing_page_url	https://doi.org/10.1073/pnas.1513023113
publication_date	2016-05-02
publication_year	2016
referenced_works	https://openalex.org/W1993646374, https://openalex.org/W2046155010, https://openalex.org/W2042195196, https://openalex.org/W1996415286, https://openalex.org/W2009928329, https://openalex.org/W1997667014, https://openalex.org/W2033796363, https://openalex.org/W1995184255, https://openalex.org/W1978538506, https://openalex.org/W2025024828, https://openalex.org/W2064744782, https://openalex.org/W35099944, https://openalex.org/W2164753229, https://openalex.org/W2147059038, https://openalex.org/W2001039490, https://openalex.org/W2028048360, https://openalex.org/W2059784252, https://openalex.org/W2026748545, https://openalex.org/W2035902938, https://openalex.org/W2131058993, https://openalex.org/W2136388877, https://openalex.org/W2060408216, https://openalex.org/W77849655, https://openalex.org/W1544298449, https://openalex.org/W2023262488, https://openalex.org/W2047849624, https://openalex.org/W2142972231, https://openalex.org/W2008178751, https://openalex.org/W2043510184, https://openalex.org/W1970009324, https://openalex.org/W2129455301, https://openalex.org/W2054525948, https://openalex.org/W2042427553, https://openalex.org/W1997827764, https://openalex.org/W2010612779, https://openalex.org/W2033447440, https://openalex.org/W2052322970, https://openalex.org/W1981894827, https://openalex.org/W2081808783, https://openalex.org/W1990381590, https://openalex.org/W1994848449, https://openalex.org/W2141709979, https://openalex.org/W2083457841, https://openalex.org/W2086941386, https://openalex.org/W2012730900, https://openalex.org/W1971293891, https://openalex.org/W2145335139, https://openalex.org/W2165404127, https://openalex.org/W2054371666, https://openalex.org/W2157892560, https://openalex.org/W2156378819, https://openalex.org/W1973324960, https://openalex.org/W2022256282, https://openalex.org/W2071609853, https://openalex.org/W2171313739, https://openalex.org/W1965447388, https://openalex.org/W2115885368, https://openalex.org/W156996324, https://openalex.org/W1533172840
referenced_works_count	59
abstract_inverted_index.a	45
abstract_inverted_index.2.	21
abstract_inverted_index.It	22
abstract_inverted_index.We	40
abstract_inverted_index.be	37, 93, 108
abstract_inverted_index.by	69
abstract_inverted_index.in	110, 114
abstract_inverted_index.is	31
abstract_inverted_index.it	35
abstract_inverted_index.of	5, 59
abstract_inverted_index.150	2
abstract_inverted_index.all	60
abstract_inverted_index.and	33, 47, 54, 66, 106
abstract_inverted_index.can	36
abstract_inverted_index.for	17
abstract_inverted_index.may	107
abstract_inverted_index.not	92
abstract_inverted_index.the	8, 61
abstract_inverted_index.yet	73
abstract_inverted_index.High	95
abstract_inverted_index.IGF2	75, 78, 96, 112
abstract_inverted_index.cell	104
abstract_inverted_index.site	89
abstract_inverted_index.that	50, 87
abstract_inverted_index.this	26
abstract_inverted_index.were	64, 84
abstract_inverted_index.when	71
abstract_inverted_index.with	81
abstract_inverted_index.could	91, 100
abstract_inverted_index.loops	16, 63, 83
abstract_inverted_index.these	42
abstract_inverted_index.using	44
abstract_inverted_index.years	4
abstract_inverted_index.During	1
abstract_inverted_index.factor	20
abstract_inverted_index.growth	19
abstract_inverted_index.highly	27
abstract_inverted_index.ligand	29
abstract_inverted_index.applied	109
abstract_inverted_index.binding	15, 62, 82, 88, 98
abstract_inverted_index.cancer.	115
abstract_inverted_index.display	53
abstract_inverted_index.domains	99
abstract_inverted_index.evolved	13, 28
abstract_inverted_index.further	38
abstract_inverted_index.inhibit	102
abstract_inverted_index.mannose	10
abstract_inverted_index.million	3
abstract_inverted_index.protein	55
abstract_inverted_index.remains	23
abstract_inverted_index.surface	52, 79
abstract_inverted_index.unknown	24
abstract_inverted_index.whether	25, 34
abstract_inverted_index.100-fold	70
abstract_inverted_index.Multiple	57
abstract_inverted_index.affinity	68, 97
abstract_inverted_index.evolved.	39
abstract_inverted_index.improved	67
abstract_inverted_index.mutation	46
abstract_inverted_index.optimal,	32
abstract_inverted_index.receptor	12
abstract_inverted_index.retained	74
abstract_inverted_index.strategy	49
abstract_inverted_index.addressed	41
abstract_inverted_index.combined,	72
abstract_inverted_index.evolution	90
abstract_inverted_index.mammalian	6
abstract_inverted_index.mutations	58
abstract_inverted_index.questions	43
abstract_inverted_index.reshaped,	85
abstract_inverted_index.selection	48
abstract_inverted_index.targeting	113
abstract_inverted_index.evolution,	7
abstract_inverted_index.identified	65
abstract_inverted_index.indicating	86
abstract_inverted_index.predicted.	94
abstract_inverted_index.signaling,	105
abstract_inverted_index.structure.	56
abstract_inverted_index.6-phosphate	11
abstract_inverted_index.interaction	30
abstract_inverted_index.selectively	101
abstract_inverted_index.therapeutic	111
abstract_inverted_index.Significance	0
abstract_inverted_index.incorporated	51
abstract_inverted_index.insulin-like	18
abstract_inverted_index.interactions	80
abstract_inverted_index.specificity.	76
abstract_inverted_index.Structurally,	77
abstract_inverted_index.high-affinity	14
abstract_inverted_index.IGF2-dependent	103
abstract_inverted_index.membrane-bound	9
cited_by_percentile_year.max	98
cited_by_percentile_year.min	89
countries_distinct_count	1
institutions_distinct_count	17
sustainable_development_goals[0].id	https://metadata.un.org/sdg/3
sustainable_development_goals[0].score	0.550000011920929
sustainable_development_goals[0].display_name	Good health and well-being
citation_normalized_percentile.value	0.89655483
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	True