ジャーナル: Cell Rep / 年: 2020 タイトル: A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms. 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 / 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.
G: SIgN-3C Fab heavy chain I: SIgN-3C Fab light chain B: Dengue virus serotype 2 E protein E: Dengue virus serotype 2 M protein A: Dengue virus serotype 2 E protein D: Dengue virus serotype 2 M protein C: Dengue virus serotype 2 E protein F: Dengue virus serotype 2 M protein H: SIgN-3C Fab heavy chain L: SIgN-3C Fab light chain ヘテロ分子
G: SIgN-3C Fab heavy chain I: SIgN-3C Fab light chain B: Dengue virus serotype 2 E protein E: Dengue virus serotype 2 M protein A: Dengue virus serotype 2 E protein D: Dengue virus serotype 2 M protein C: Dengue virus serotype 2 E protein F: Dengue virus serotype 2 M protein H: SIgN-3C Fab heavy chain L: SIgN-3C Fab light chain ヘテロ分子
G: SIgN-3C Fab heavy chain I: SIgN-3C Fab light chain B: Dengue virus serotype 2 E protein E: Dengue virus serotype 2 M protein A: Dengue virus serotype 2 E protein D: Dengue virus serotype 2 M protein C: Dengue virus serotype 2 E protein F: Dengue virus serotype 2 M protein H: SIgN-3C Fab heavy chain L: SIgN-3C Fab light chain ヘテロ分子
x 5
icosahedral pentamer
1.21 MDa, 50 ポリマー
分子量 (理論値)
分子数
合計 (水以外)
1,208,016
80
ポリマ-
1,198,332
50
非ポリマー
9,684
30
水
0
タイプ
名称
対称操作
数
point symmetry operation
5
4
G: SIgN-3C Fab heavy chain I: SIgN-3C Fab light chain B: Dengue virus serotype 2 E protein E: Dengue virus serotype 2 M protein A: Dengue virus serotype 2 E protein D: Dengue virus serotype 2 M protein C: Dengue virus serotype 2 E protein F: Dengue virus serotype 2 M protein H: SIgN-3C Fab heavy chain L: SIgN-3C Fab light chain ヘテロ分子