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-Structure paper
タイトル | A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms. |
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ジャーナル・号・ページ | Cell Rep, Vol. 31, Issue 4, Page 107584, Year 2020 |
掲載日 | 2020年4月28日 |
著者 | Shuijun Zhang / Thomas Loy / Thiam-Seng Ng / Xin-Ni Lim / Shyn-Yun Valerie Chew / Ter Yong Tan / Meihui Xu / Victor A Kostyuchenko / Farhana Tukijan / Jian Shi / Katja Fink / Shee-Mei Lok / |
PubMed 要旨 | Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs ...Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endosomal conditions (pH 8.0-6.5). We observe Fab binding to DENV (pH 8.0-5.0) prevents virus fusion, and the number of bound Fabs increase (from 120 to 180). For ZIKV, although there are already 180 copies of Fab at pH 8.0, virus structural changes at pH 5.0 are not inhibited. The immunoglobulin G (IgG):DENV structure at pH 8.0 shows both Fab arms bind to epitopes around the 2-fold vertex. On ZIKV, an additional Fab around the 5-fold vertex at pH 8.0 suggests one IgG arm would engage with an epitope, although the other may bind to other viruses, causing aggregation. For DENV2 at pH 5.0, a similar scenario would occur, suggesting DENV2:IgG complex would aggregate in the endosome. Hence, a single antibody employs different neutralization mechanisms against different flaviviruses. |
リンク | Cell Rep / PubMed:32348755 |
手法 | EM (単粒子) |
解像度 | 3.8 - 7.8 Å |
構造データ | EMDB-30192, PDB-7bu8: EMDB-30193, PDB-7bua: EMDB-30194, PDB-7bub: EMDB-30195, PDB-7bud: EMDB-30196, PDB-7bue: EMDB-30197, PDB-7buf: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRUS / Zika virus / antibody / neutralization / Dengue virus |