5ANY

Electron cryo-microscopy of chikungunya virus in complex with neutralizing antibody Fab CHK265

5ANY の概要

• エントリーDOI: 10.2210/pdb5any/pdb
• 関連するPDBエントリー: 5ANX
• EMDBエントリー: 3144
• 分子名称: E1, E2, FAB CHK265, ... (4 entities in total)
• 機能のキーワード: virus, chikungunya virus, neutralizing antibody fab
• 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: 542420.87

構造登録者

Fox, J.M.,Long, F.,Edeling, M.A.,Lin, H.,Duijl-Richter, M.,Fong, R.H.,Kahle, K.M.,Smit, J.M.,Jin, J.,Simmons, G.,Doranz, B.J.,Crowe, J.E.,Fremont, D.H.,Rossmann, M.G.,Diamond, M.S. (登録日: 2015-09-08, 公開日: 2015-11-25, 最終更新日: 2024-11-13)

主引用文献

Fox, J.M.,Long, F.,Edeling, M.A.,Lin, H.,Van Duijl-Richter, M.K.S.,Fong, R.H.,Kahle, K.M.,Smit, J.M.,Jin, J.,Simmons, G.,Doranz, B.J.,Crowe, J.E.J.,Fremont, D.H.,Rossmann, M.G.,Diamond, M.S.
Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.
Cell(Cambridge,Mass.), 163:1095-, 2015

PubMed Abstract: We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern.

PubMed: 26553503
DOI: 10.1016/J.CELL.2015.10.050

実験手法

ELECTRON MICROSCOPY (16.9 Å)