EMD-43671

Single-particle
3.1 Å
EMD-43671 Deposition: 09/02/2024
Map released: 18/09/2024
Last modified: 18/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-43671

Soluble ectodomain of human cytomegalovirus (HCMV) glycoprotein B (gB) stabilized in a prefusion-like conformation in complex with 1G2 and 7H3, local refinement

EMD-43671

Single-particle
3.1 Å
EMD-43671 Deposition: 09/02/2024
Map released: 18/09/2024
Last modified: 18/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human betaherpesvirus 5
Sample: Soluble ectodomain of human cytomegalovirus (HCMV) glycoprotein B (gB) stabilized in a prefusion-like conformation in complex with 1G2 and 7H3

Deposition Authors: Sponholtz MR , Byrne PO , McLellan JS
Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.
PUBMED: 39231203
DOI: doi:10.1073/pnas.2404250121
ISSN: 1091-6490
ASTM: PNASA6
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.