5VOB

Crystal structure of HCMV Pentamer in complex with neutralizing antibody 8I21

5VOB の概要

• エントリーDOI: 10.2210/pdb5vob/pdb
• 関連するPDBエントリー: 5VOC 5VOD
• 分子名称: Envelope glycoprotein H, Envelope glycoprotein L, Envelope glycoprotein UL128, ... (9 entities in total)
• 機能のキーワード: hcmv, neutralizing epitope, immunogen, viral entry, pentamer, vaccine, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human cytomegalovirus (HHV-5); 詳細
• 細胞内の位置: Virion membrane ; Single-pass type I membrane protein : Q6SW67; Virion membrane ; Peripheral membrane protein ; Extracellular side : Q68674; Virion : F5HET4
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 236101.97

構造登録者

Malito, E.,Chandramouli, S. (登録日: 2017-05-02, 公開日: 2017-07-05, 最終更新日: 2024-11-13)

主引用文献

Chandramouli, S.,Malito, E.,Nguyen, T.,Luisi, K.,Donnarumma, D.,Xing, Y.,Norais, N.,Yu, D.,Carfi, A.
Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.
Sci Immunol, 2:-, 2017

PubMed Abstract: Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.

PubMed: 28783665
DOI: 10.1126/sciimmunol.aan1457

実験手法

X-RAY DIFFRACTION (3.02 Å)