6OTC

Synthetic Fab bound to Marburg virus VP35 interferon inhibitory domain

6OTC の概要

• エントリーDOI: 10.2210/pdb6otc/pdb
• 分子名称: Polymerase cofactor VP35, sFab H3 heavy chain, sFab H3 light chain, ... (6 entities in total)
• 機能のキーワード: marburg virus, fab, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Lake Victoria marburgvirus (strain Popp-67) (MARV); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65360.52

構造登録者

Amatya, P.,Chen, G.,Borek, D.,Sidhu, S.S.,Leung, D.W. (登録日: 2019-05-02, 公開日: 2019-06-05, 最終更新日: 2024-10-09)

主引用文献

Amatya, P.,Wagner, N.,Chen, G.,Luthra, P.,Shi, L.,Borek, D.,Pavlenco, A.,Rohrs, H.,Basler, C.F.,Sidhu, S.S.,Gross, M.L.,Leung, D.W.
Inhibition of Marburg Virus RNA Synthesis by a Synthetic Anti-VP35 Antibody.
Acs Infect Dis., 5:1385-1396, 2019

PubMed Abstract: Marburg virus causes sporadic outbreaks of severe hemorrhagic fever with high case fatality rates. Approved, effective, and safe therapeutic or prophylactic countermeasures are lacking. To address this, we used phage display to engineer a synthetic antibody, sFab H3, which binds the Marburg virus VP35 protein (mVP35). mVP35 is a critical cofactor of the viral replication complex and a viral immune antagonist. sFab H3 displayed high specificity for mVP35 and not for the closely related Ebola virus VP35. sFab H3 inhibited viral-RNA synthesis in a minigenome assay, suggesting its potential use as an antiviral. We characterized sFab H3 by a combination of biophysical and biochemical methods, and a crystal structure of the complex solved to 1.7 Å resolution defined the molecular interface between the sFab H3 and mVP35 interferon inhibitory domain. Our study identifies mVP35 as a therapeutic target using an approach that provides a framework for generating engineered Fabs targeting other viral proteins.

PubMed: 31120240
DOI: 10.1021/acsinfecdis.9b00091

実験手法

X-RAY DIFFRACTION (1.7 Å)