8COI
Human adenovirus-derived synthetic ADDobody binder
Summary for 8COI
| Entry DOI | 10.2210/pdb8coi/pdb |
| Descriptor | ADDobody (1 entity in total) |
| Functional Keywords | penton base, crown domain, human adenovirus, viral protein |
| Biological source | Human adenovirus sp. |
| Total number of polymer chains | 20 |
| Total formula weight | 704970.24 |
| Authors | Buzas, D.,Toelzer, C.,Gupta, K.,Berger-Schaffitzel, C.,Berger, I. (deposition date: 2023-02-28, release date: 2023-12-27, Last modification date: 2024-03-20) |
| Primary citation | Buzas, D.,Sun, H.,Toelzer, C.,Yadav, S.K.N.,Borucu, U.,Gautam, G.,Gupta, K.,Bufton, J.C.,Capin, J.,Sessions, R.B.,Garzoni, F.,Berger, I.,Schaffitzel, C. Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders. Structure, 32:342-, 2024 Cited by 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-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. PubMed: 38198950DOI: 10.1016/j.str.2023.12.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.17 Å) |
Structure validation
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