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-Structure paper
| タイトル | Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics. |
|---|---|
| ジャーナル・号・ページ | Cell, Vol. 184, Issue 25, Page 6067-6080.e13, Year 2021 |
| 掲載日 | 2021年12月9日 |
著者 | Xin-Xiang Lim / Bo Shu / Shuijun Zhang / Aaron W K Tan / Thiam-Seng Ng / Xin-Ni Lim / Valerie S-Y Chew / Jian Shi / Gavin R Screaton / Shee-Mei Lok / Ganesh S Anand / ![]() |
| PubMed 要旨 | The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 ...The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 (DENV2) particles by cryoelectron microscopy (cryo-EM) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS) shows that Fab C10 binding decreases overall ZIKV particle dynamics, whereas with DENV2, the same Fab causes increased dynamics. Testing of different Fab C10:DENV2 E protein molar ratios revealed that, at higher Fab ratios, especially at saturated concentrations, the Fab enhanced viral dynamics (detected by HDXMS), and observation under cryo-EM showed increased numbers of distorted particles. Our results suggest that Fab C10 stabilizes ZIKV but that with DENV2 particles, high Fab C10 occupancy promotes E protein dimer conformational changes leading to overall increased particle dynamics and distortion of the viral surface. This is the first instance of a broadly neutralizing antibody eliciting virus-specific increases in whole virus particle dynamics. |
リンク | Cell / PubMed:34852238 |
| 手法 | EM (単粒子) |
| 解像度 | 3.1 - 4.9 Å |
| 構造データ | EMDB-31677, PDB-7v3f: EMDB-31678, PDB-7v3g: EMDB-31679, PDB-7v3h: EMDB-31680, PDB-7v3i: EMDB-31681, PDB-7v3j: ![]() EMDB-31682: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | VIRUS / virus complexed with antibody / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex / complex / antibody / complexed / IMMUNE SYSTEM/VIRUS / IMMUNE SYSTEM-VIRUS complex |
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dengue virus type 2 (strain thailand/ngs-c/1944) (デング熱ウイルス)
homo sapiens (ヒト)
キーワード