7CVZ

Cryo-EM structure of Chikungunya virus in complex with Fab fragments of mAb CHK-263

7CVZ の概要

• エントリーDOI: 10.2210/pdb7cvz/pdb
• EMDBエントリー: 30476 30477
• 分子名称: E1 glycoprotein, E2 glycoprotein, Capsid protein, ... (5 entities in total)
• 機能のキーワード: virus, fab, complex, virus-immune system complex, virus/immune system
• 由来する生物種: Chikungunya virus; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 535853.21

構造登録者

Zhou, Q.F.,Fox, J.M.,Earnest, J.T.,Ng, T.S.,Kim, A.S.,Fibriansah, G.,Kostyuchenko, V.A.,Shu, B.,Diamond, M.S.,Lok, S.M. (登録日: 2020-08-27, 公開日: 2020-11-04, 最終更新日: 2024-03-27)

主引用文献

Zhou, Q.F.,Fox, J.M.,Earnest, J.T.,Ng, T.S.,Kim, A.S.,Fibriansah, G.,Kostyuchenko, V.A.,Shi, J.,Shu, B.,Diamond, M.S.,Lok, S.M.
Structural basis of Chikungunya virus inhibition by monoclonal antibodies.
Proc.Natl.Acad.Sci.USA, 117:27637-27645, 2020

PubMed Abstract: Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral infection. CHK-124 aggregates virus particles and blocks attachment. Also, due to antibody-induced virus aggregation, fusion with endosomes and egress are inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus attachment and fusion. To determine the structural basis of neutralization, we generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that spans across E1 and E2 and locks the heterodimer together, likely preventing structural rearrangements required for fusion. These results provide structural insight as to how neutralizing antibody engagement of CHIKV inhibits different stages of the viral life cycle, which could inform vaccine and therapeutic design.

PubMed: 33087569
DOI: 10.1073/pnas.2008051117

実験手法

ELECTRON MICROSCOPY (4.7 Å)