8QBX

Chimeric Adenovirus-derived dodecamer

This is a non-PDB format compatible entry.

Summary for 8QBX

• Entry DOI: 10.2210/pdb8qbx/pdb
• EMDB information: 18323
• Descriptor: Penton protein (1 entity in total)
• Functional Keywords: adenovirus, capsid protein, virus-like particle, virus like particle
• Biological source: Human adenovirus sp.
• Total number of polymer chains: 60
• Total formula weight: 3791748.72

Authors

Buzas, D.,Borucu, U.,Bufton, J.,Kapadalakere, S.Y.,Toelzer, C. (deposition date: 2023-08-25, 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

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: 38198950
DOI: 10.1016/j.str.2023.12.010

Experimental method

ELECTRON MICROSCOPY (2.2 Å)