8VYM

Soluble ectodomain of human cytomegalovirus (HCMV) glycoprotein B (gB) in the postfusion conformation in complex with 1G2 and 7H3 Fabs

8VYM の概要

• エントリーDOI: 10.2210/pdb8vym/pdb
• EMDBエントリー: 43667
• 分子名称: Envelope glycoprotein B, 1G2 Fab Heavy Chain, 1G2 Fab Light Chain, ... (8 entities in total)
• 機能のキーワード: orthoherpesvirus, betaherpesvirus, cytomegalovirus, human betaherpesvirus 5, human cytomegalovirus, hcmv, glycoprotein b, gb, hcmv gb, viral protein, 7h3, 1g2, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human betaherpesvirus 5; 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 465492.55

構造登録者

Sponholtz, M.R.,Byrne, P.O.,McLellan, J.S. (登録日: 2024-02-09, 公開日: 2024-09-18, 最終更新日: 2025-06-04)

主引用文献

Sponholtz, M.R.,Byrne, P.O.,Lee, A.G.,Ramamohan, A.R.,Goldsmith, J.A.,McCool, R.S.,Zhou, L.,Johnson, N.V.,Hsieh, C.L.,Connors, M.,Karthigeyan, K.P.,Crooks, C.M.,Fuller, A.S.,Campbell, J.D.,Permar, S.R.,Maynard, J.A.,Yu, D.,Bottomley, M.J.,McLellan, J.S.
Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.
Proc.Natl.Acad.Sci.USA, 121:e2404250121-e2404250121, 2024

PubMed Abstract: Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.

PubMed: 39231203
DOI: 10.1073/pnas.2404250121

実験手法

ELECTRON MICROSCOPY (3.4 Å)