7KDP

HCMV prefusion gB in complex with fusion inhibitor WAY-174865

7KDP の概要

• エントリーDOI: 10.2210/pdb7kdp/pdb
• EMDBエントリー: 22828
• 分子名称: Envelope glycoprotein B, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-{4-[({(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}carbamothioyl)amino]phenyl}-1,3-thiazole-4-carboxamide, ... (4 entities in total)
• 機能のキーワード: fusogen, prefusion, hcmv, gb, antibody, viral protein, fusion inhibitor, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Human cytomegalovirus (strain Towne) (HHV-5)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 314434.88

構造登録者

Liu, Y.,Heim, P.K.,Che, Y.,Chi, X.,Qiu, X.,Han, S.,Dormitzer, P.R.,Yang, X. (登録日: 2020-10-09, 公開日: 2021-03-17, 最終更新日: 2024-11-13)

主引用文献

Liu, Y.,Heim, K.P.,Che, Y.,Chi, X.,Qiu, X.,Han, S.,Dormitzer, P.R.,Yang, X.
Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion.
Sci Adv, 7:-, 2021

PubMed Abstract: Human cytomegalovirus (HCMV) causes congenital disease with long-term morbidity. HCMV glycoprotein B (gB) transitions irreversibly from a metastable prefusion to a stable postfusion conformation to fuse the viral envelope with a host cell membrane during entry. We stabilized prefusion gB on the virion with a fusion inhibitor and a chemical cross-linker, extracted and purified it, and then determined its structure to 3.6-Å resolution by electron cryomicroscopy. Our results revealed the structural rearrangements that mediate membrane fusion and details of the interactions among the fusion loops, the membrane-proximal region, transmembrane domain, and bound fusion inhibitor that stabilized gB in the prefusion state. The structure rationalizes known gB antigenic sites. By analogy to successful vaccine antigen engineering approaches for other viral pathogens, the high-resolution prefusion gB structure provides a basis to develop stabilized prefusion gB HCMV vaccine antigens.

PubMed: 33674318
DOI: 10.1126/sciadv.abf3178

実験手法

ELECTRON MICROSCOPY (3.6 Å)