{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Buzas D"],"funding":["European Research Council","Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["342-351.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616808"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(3)"],"pubmed_abstract":["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 ∼10<sup>4</sup>-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."],"journal":["Structure (London, England : 1993)"],"pubmed_title":["Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders."],"pmcid":["PMC7616808"],"funding_grant_id":["221708","BB/R000484/1","202904/Z/16/Z","106115/Z/14/Z","206181/Z/17/Z","210701/Z/18/Z","221708/Z/20/Z","834631"],"pubmed_authors":["Capin J","Yadav SKN","Berger I","Gautam G","Sessions RB","Bufton JC","Toelzer C","Buzas D","Gupta K","Sun H","Garzoni F","Schaffitzel C","Borucu U"],"additional_accession":[]},"is_claimable":false,"name":"Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders.","description":"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 ∼10<sup>4</sup>-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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-21T03:10:02.632Z","creation":"2025-04-21T21:48:52.284Z"},"accession":"S-EPMC7616808","cross_references":{"pubmed":["38198950"],"doi":["10.1016/j.str.2023.12.010"]}}