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TitleA noncanonical glycoprotein H complex enhances cytomegalovirus entry.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateOct 13, 2024
AuthorsMichael J Norris / Lauren A Henderson / Mohammed N A Siddiquey / Jieyun Yin / Kwangsun Yoo / Simon Brunel / Erica Ollmann Saphire / Chris A Benedict / Jeremy P Kamil /
PubMed AbstractHuman cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the ...Human cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the incomplete understanding of the diverse protein complexes the virus uses to infect cells. In , the gH/gL glycoprotein heterodimer is expected to be a basal element of virion cell entry machinery. For HCMV, gH/gL forms a "trimer" with gO and a "pentamer" with UL128, UL130, and UL131A, with each complex binding distinct receptors to enter varied cell types. Here, we reveal a third glycoprotein complex, abundant in HCMV virions, which significantly enhances infection of endothelial cells. In this "3-mer" complex, gH, without gL, associates with UL116 and UL141, an immunoevasin previously known to function in an intracellular role. Cryo-EM reveals the virion-surface 3-mer is structurally unique among gH complexes, with gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. Given that antibodies directed at gH and UL141 each can restrict HCMV replication, our work highlights this virion surface complex as a new target for vaccines and antiviral therapies.
External linksbioRxiv / PubMed:39416215 / PubMed Central
MethodsEM (single particle)
Resolution3.51 - 5.36 Å
Structure data

46920

9dix

EMDB-46920, PDB-9dix:
HCMV gH/UL116/UL141 3-mer complex, ectodomain
Method: EM (single particle) / Resolution: 3.51 Å

46921

9diy

EMDB-46921, PDB-9diy:
Local Cryo-EM structure of HCMV gH/UL116 interaction
Method: EM (single particle) / Resolution: 5.36 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human betaherpesvirus 5
KeywordsVIRAL PROTEIN / Surface protein complex

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