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TitlePrefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion.
Journal, issue, pagesSci Adv, Vol. 7, Issue 10, Year 2021
Publish dateMar 5, 2021
AuthorsYuhang Liu / Kyle P Heim / Ye Che / Xiaoyuan Chi / Xiayang Qiu / Seungil Han / Philip R Dormitzer / Xinzhen Yang /
PubMed AbstractHuman 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 ...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.
External linksSci Adv / PubMed:33674318 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.6 Å
Structure data

22819

7kdd

EMDB-22819, PDB-7kdd:
HCMV postfusion gB in complex with SM5-1 Fab
Method: EM (single particle) / Resolution: 3.5 Å

22828

7kdp

EMDB-22828, PDB-7kdp:
HCMV prefusion gB in complex with fusion inhibitor WAY-174865
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CA:
Unknown entry

ChemComp-WCY:
N-{4-[({(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}carbamothioyl)amino]phenyl}-1,3-thiazole-4-carboxamide

Source
  • human cytomegalovirus (strain towne)
  • homo sapiens (human)
  • HHV-5 (virus)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / fusogen / postfusion / HCMV / gB / antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN/INHIBITOR / prefusion / fusion inhibitor / VIRAL PROTEIN-INHIBITOR complex

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