6MID

Cryo-EM structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195

6MID の概要

• エントリーDOI: 10.2210/pdb6mid/pdb
• EMDBエントリー: 9131
• 分子名称: E protein, M protein, monoclonal antibody ZIKV-195 heavy chain, ... (5 entities in total)
• 機能のキーワード: virus, monoclonal antibody, complex, virus-immune system complex, virus/immune system
• 由来する生物種: Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013) (ZIKV); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 215995.65

構造登録者

Long, F.,Rossmann, M.G. (登録日: 2018-09-19, 公開日: 2019-01-16, 最終更新日: 2024-10-23)

主引用文献

Long, F.,Doyle, M.,Fernandez, E.,Miller, A.S.,Klose, T.,Sevvana, M.,Bryan, A.,Davidson, E.,Doranz, B.J.,Kuhn, R.J.,Diamond, M.S.,Crowe Jr., J.E.,Rossmann, M.G.
Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope.
Proc. Natl. Acad. Sci. U.S.A., 116:1591-1596, 2019

PubMed Abstract: Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.

PubMed: 30642974
DOI: 10.1073/pnas.1815432116

実験手法

ELECTRON MICROSCOPY (4 Å)