Asymmetric binding of coactivator SRC1 to FXR-RXR and allosteric communication within the complex Article Swipe
Yanan Sheng
,
Yaoting Guo
,
Sun Mingze
,
Yan Dong
,
Yue Yin
,
Yan‐Wu Wang
,
Chao Peng
,
Yong Xu
,
Na Wang
,
Jinsong Liu
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.05.13.593894
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.05.13.593894
Farnesoid X receptor (FXR) is a promising target for treatment of metabolic associated fatty liver disease (MAFLD). In this study, we employed an integrative approach to investigate the interaction between FXR-RXRα-hSHP-1 complex and the entire coactivator SRC1-NRID (nuclear receptor interaction domain). We constructed a multi-domain model of FXR 120 -RXRα 98 -hSHP-1, highlighting the interface between FXR-DBD and LBD. Using HDX-MS, XL-MS, and biochemical assays, we revealed the allosteric communications in FXR-RXRα-hSHP-1 upon agonist and DNA binding. We then demonstrated that SRC1 binds only to the coactivator binding surface of FXR within the FXR-RXRα heterodimer, with the NR-box2 and NR-box3 of SRC1 as the key binding motifs. Our findings, which provide the first model of SRC1-NRID in complex with FXR-RXRα-hSHP-1, shed light on the molecular mechanism through which the coactivator asymmetrically interacts with nuclear receptors and provide structural basis for further understanding the function of FXR and its implications in diseases.
Related Topics
Concepts
Coactivator
Farnesoid X receptor
Nuclear receptor coactivator 1
Nuclear receptor
Chemistry
Allosteric regulation
Nuclear receptor coactivator 2
Retinoid X receptor
Cell biology
Cancer research
Receptor
Biochemistry
Biophysics
Transcription factor
Biology
Gene
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.05.13.593894
- https://www.biorxiv.org/content/biorxiv/early/2024/05/13/2024.05.13.593894.full.pdf
- OA Status
- green
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396872693
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4396872693Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2024.05.13.593894Digital Object Identifier
- Title
-
Asymmetric binding of coactivator SRC1 to FXR-RXR and allosteric communication within the complexWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2024Year of publication
- Publication date
-
2024-05-13Full publication date if available
- Authors
-
Yanan Sheng, Yaoting Guo, Sun Mingze, Yan Dong, Yue Yin, Yan‐Wu Wang, Chao Peng, Yong Xu, Na Wang, Jinsong LiuList of authors in order
- Landing page
-
https://doi.org/10.1101/2024.05.13.593894Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/05/13/2024.05.13.593894.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/05/13/2024.05.13.593894.full.pdfDirect OA link when available
- Concepts
-
Coactivator, Farnesoid X receptor, Nuclear receptor coactivator 1, Nuclear receptor, Chemistry, Allosteric regulation, Nuclear receptor coactivator 2, Retinoid X receptor, Cell biology, Cancer research, Receptor, Biochemistry, Biophysics, Transcription factor, Biology, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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53Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.receptor | 3, 39 |
| abstract_inverted_index.revealed | 67 |
| abstract_inverted_index.FXR-RXRα | 94 |
| abstract_inverted_index.Farnesoid | 1 |
| abstract_inverted_index.SRC1-NRID | 37, 116 |
| abstract_inverted_index.diseases. | 151 |
| abstract_inverted_index.findings, | 109 |
| abstract_inverted_index.interacts | 132 |
| abstract_inverted_index.interface | 55 |
| abstract_inverted_index.mechanism | 126 |
| abstract_inverted_index.metabolic | 12 |
| abstract_inverted_index.molecular | 125 |
| abstract_inverted_index.promising | 7 |
| abstract_inverted_index.receptors | 135 |
| abstract_inverted_index.treatment | 10 |
| abstract_inverted_index.allosteric | 69 |
| abstract_inverted_index.associated | 13 |
| abstract_inverted_index.structural | 138 |
| abstract_inverted_index.biochemical | 64 |
| abstract_inverted_index.coactivator | 36, 87, 130 |
| abstract_inverted_index.constructed | 43 |
| abstract_inverted_index.integrative | 24 |
| abstract_inverted_index.interaction | 29, 40 |
| abstract_inverted_index.investigate | 27 |
| abstract_inverted_index.demonstrated | 80 |
| abstract_inverted_index.heterodimer, | 95 |
| abstract_inverted_index.highlighting | 53 |
| abstract_inverted_index.implications | 149 |
| abstract_inverted_index.multi-domain | 45 |
| abstract_inverted_index.understanding | 142 |
| abstract_inverted_index.asymmetrically | 131 |
| abstract_inverted_index.communications | 70 |
| abstract_inverted_index.FXR-RXRα-hSHP-1 | 31, 72 |
| abstract_inverted_index.FXR-RXRα-hSHP-1, | 120 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5100461406, https://openalex.org/A5100611766 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I126520041, https://openalex.org/I19820366, https://openalex.org/I2802148028, https://openalex.org/I4210154954 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7599999904632568 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.0969835 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |