National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01A102546
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM079429
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41GM103832
米国
National Institutes of Health/Office of the Director
S10OD021600
米国
引用
ジャーナル: Nat Commun / 年: 2020 タイトル: A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation. 著者: Stefan L Oliver / Yi Xing / Dong-Hua Chen / Soung Hun Roh / Grigore D Pintilie / David A Bushnell / Marvin H Sommer / Edward Yang / Andrea Carfi / Wah Chiu / Ann M Arvin / 要旨: Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells ...Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells to form polykaryocytes in infected tissues. The conserved glycoproteins, gB, gH and gL, are the core functional proteins of the herpesvirus fusion complex. gB serves as the primary fusogen via its fusion loops, but functions for the remaining gB domains remain unexplained. As a pathway for biological discovery of domain function, our approach used structure-based analysis of the viral fusogen together with a neutralizing antibody. We report here a 2.8 Å cryogenic-electron microscopy structure of native gB recovered from VZV-infected cells, in complex with a human monoclonal antibody, 93k. This high-resolution structure guided targeted mutagenesis at the gB-93k interface, providing compelling evidence that a domain spatially distant from the gB fusion loops is critical for herpesvirus fusion, revealing a potential new target for antiviral therapies.
全体 : Varicella zoster virus glycoprotein B in complex with Fab fragmen...
全体
名称: Varicella zoster virus glycoprotein B in complex with Fab fragments derived from human monoclonal antibody 93k
要素
複合体: Varicella zoster virus glycoprotein B in complex with Fab fragments derived from human monoclonal antibody 93k
複合体: human monoclonal antibody 93k Fab
タンパク質・ペプチド: Human monoclonal antibody 93k variable light chain
タンパク質・ペプチド: Human monoclonal antibody 93k variable heavy chain
複合体: Varicella zoster virus glycoprotein B
タンパク質・ペプチド: Envelope glycoprotein B
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超分子 #1: Varicella zoster virus glycoprotein B in complex with Fab fragmen...
超分子
名称: Varicella zoster virus glycoprotein B in complex with Fab fragments derived from human monoclonal antibody 93k タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
分子量
実験値: 750 KDa
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超分子 #2: human monoclonal antibody 93k Fab
超分子
名称: human monoclonal antibody 93k Fab / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#2