9DIY

Local Cryo-EM structure of HCMV gH/UL116 interaction

Summary for 9DIY

• Entry DOI: 10.2210/pdb9diy/pdb
• EMDB information: 46921
• Descriptor: Envelope glycoprotein H, UL116, Protein UL141, ... (6 entities in total)
• Functional Keywords: surface protein complex, viral protein
• Biological source: Human betaherpesvirus 5; More
• Total number of polymer chains: 3
• Total formula weight: 146859.93

Authors

Norris, M.J.,Benedict, C.A.,Kamil, J.P.,Saphire, E.O. (deposition date: 2024-09-06, release date: 2024-11-20)

Primary citation

Norris, M.J.,Henderson, L.A.,Siddiquey, M.N.A.,Yin, J.,Yoo, K.,Brunel, S.,Saphire, E.O.,Benedict, C.A.,Kamil, J.P.
A noncanonical glycoprotein H complex enhances cytomegalovirus entry.
Biorxiv, 2024

PubMed Abstract: 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.

PubMed: 39416215
DOI: 10.1101/2024.10.13.617647
PDB entries with the same primary citation

Experimental method

ELECTRON MICROSCOPY (5.36 Å)