8COI

Human adenovirus-derived synthetic ADDobody binder

8COI の概要

• エントリーDOI: 10.2210/pdb8coi/pdb
• 分子名称: ADDobody (1 entity in total)
• 機能のキーワード: penton base, crown domain, human adenovirus, viral protein
• 由来する生物種: Human adenovirus sp.
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 704970.24

構造登録者

Buzas, D.,Toelzer, C.,Gupta, K.,Berger-Schaffitzel, C.,Berger, I. (登録日: 2023-02-28, 公開日: 2023-12-27, 最終更新日: 2024-03-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.17 Å)