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)
P41GM103832
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM079429
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.
#256 - 2021年4月 SARSコロナウイルス2型のスパイクと抗体 (SARS-CoV-2 Spike and Antibodies) 類似性 (1)
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L: Human monoclonal antibody 93k variable light chain H: Human monoclonal antibody 93k variable heavy chain A: Envelope glycoprotein B M: Human monoclonal antibody 93k variable light chain I: Human monoclonal antibody 93k variable heavy chain B: Envelope glycoprotein B N: Human monoclonal antibody 93k variable light chain J: Human monoclonal antibody 93k variable heavy chain C: Envelope glycoprotein B