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-Structure paper
タイトル | A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 4141, Year 2020 |
掲載日 | 2020年8月18日 |
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 / |
PubMed 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. |
リンク | Nat Commun / PubMed:32811830 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.4529 - 2.8 Å |
構造データ | EMDB-21247, PDB-6vn1: PDB-6vlk: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN / viral membrane glycoprotein / VIRAL PROTEIN/IMMUNE SYSTEM / Varicella Zoster Virus / Glycoprotein B / Neutralization / Monoclonal Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |