Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders Article Swipe
Dora Buzas
,
Huan Sun
,
Christine Toelzer
,
Sathish K.N. Yadav
,
Ufuk Borucu
,
Gunjan Gautam
,
Kapil Gupta
,
Joshua C. Bufton
,
Julien Capin
,
Richard B. Sessions
,
Frédéric Garzoni
,
Imre Berger
,
Christiane Schaffitzel
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.str.2023.12.010
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.str.2023.12.010
Adenovirus-derived nanoparticles (ADDomer) comprise 60 copies of adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport, and deployment of ADDomer-based therapeutics independent of a cold chain. To expand the scope of ADDomers for new applications, we engineered ADDobodies, representing PBP crown domain, genetically separated from PBP multimerization domain. We inserted heterologous sequences into hyper-variable loops, resulting in monomeric, thermostable ADDobodies expressed at high yields in Escherichia coli. The X-ray structure of an ADDobody prototype validated our design. ADDobodies can be used in ribosome display experiments to select a specific binder against a target, with an enrichment factor of ∼104-fold per round. ADDobodies can be re-converted into ADDomers by genetically reconnecting the selected ADDobody with the PBP multimerization domain from a different species, giving rise to a multivalent nanoparticle, called Chimera, confirmed by a 2.2 Å electron cryo-microscopy structure. Chimera comprises 60 binding sites, resulting in ultra-high, picomolar avidity to the target.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.str.2023.12.010
- http://www.cell.com/article/S0969212623004513/pdf
- OA Status
- hybrid
- Cited By
- 3
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390743468
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4390743468Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.str.2023.12.010Digital Object Identifier
- Title
-
Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-bindersWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-09Full publication date if available
- Authors
-
Dora Buzas, Huan Sun, Christine Toelzer, Sathish K.N. Yadav, Ufuk Borucu, Gunjan Gautam, Kapil Gupta, Joshua C. Bufton, Julien Capin, Richard B. Sessions, Frédéric Garzoni, Imre Berger, Christiane SchaffitzelList of authors in order
- Landing page
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https://doi.org/10.1016/j.str.2023.12.010Publisher landing page
- PDF URL
-
https://www.cell.com/article/S0969212623004513/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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-
https://www.cell.com/article/S0969212623004513/pdfDirect OA link when available
- Concepts
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Chimera (genetics), Avidity, Protein engineering, Heterologous, Escherichia coli, Chemistry, Computational biology, Synthetic biology, Biophysics, Genetically engineered, Cell biology, Molecular biology, Biology, Biochemistry, Genetics, Gene, Antigen, EnzymeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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57Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.comprises | 142 |
| abstract_inverted_index.confirmed | 133 |
| abstract_inverted_index.different | 123 |
| abstract_inverted_index.expressed | 63 |
| abstract_inverted_index.picomolar | 149 |
| abstract_inverted_index.prototype | 76 |
| abstract_inverted_index.rendering | 15 |
| abstract_inverted_index.resulting | 58, 146 |
| abstract_inverted_index.separated | 46 |
| abstract_inverted_index.sequences | 54 |
| abstract_inverted_index.structure | 72 |
| abstract_inverted_index.validated | 77 |
| abstract_inverted_index.ADDobodies | 62, 80, 104 |
| abstract_inverted_index.adenovirus | 7 |
| abstract_inverted_index.deployment | 20 |
| abstract_inverted_index.engineered | 39 |
| abstract_inverted_index.enrichment | 98 |
| abstract_inverted_index.monomeric, | 60 |
| abstract_inverted_index.structure. | 140 |
| abstract_inverted_index.transport, | 18 |
| abstract_inverted_index.ADDobodies, | 40 |
| abstract_inverted_index.Escherichia | 68 |
| abstract_inverted_index.experiments | 87 |
| abstract_inverted_index.genetically | 45, 111 |
| abstract_inverted_index.independent | 24 |
| abstract_inverted_index.multivalent | 129 |
| abstract_inverted_index.ultra-high, | 148 |
| abstract_inverted_index.heterologous | 53 |
| abstract_inverted_index.re-converted | 107 |
| abstract_inverted_index.reconnecting | 112 |
| abstract_inverted_index.representing | 41 |
| abstract_inverted_index.therapeutics | 23 |
| abstract_inverted_index.thermostable | 61 |
| abstract_inverted_index.ADDomer-based | 22 |
| abstract_inverted_index.applications, | 37 |
| abstract_inverted_index.nanoparticle, | 130 |
| abstract_inverted_index.nanoparticles | 1 |
| abstract_inverted_index.thermostable, | 14 |
| abstract_inverted_index.hyper-variable | 56 |
| abstract_inverted_index.cryo-microscopy | 139 |
| abstract_inverted_index.multimerization | 49, 119 |
| abstract_inverted_index.Adenovirus-derived | 0 |
| abstract_inverted_index.∼10<sup>4</sup>-fold | 101 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5091178241, https://openalex.org/A5013799671 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I36234482, https://openalex.org/I4210149754 |
| citation_normalized_percentile.value | 0.74380111 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |