Structural highlights
Function
GH_HCMVM The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane fusion is mediated by the fusion machinery composed of gB and the heterodimer gH/gL. May also be involved in the fusion between the virion envelope and the outer nuclear membrane during virion morphogenesis.
Publication Abstract from PubMed
Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV.
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.,Kschonsak M, Johnson MC, Schelling R, Green EM, Rouge L, Ho H, Patel N, Kilic C, Kraft E, Arthur CP, Rohou AL, Comps-Agrar L, Martinez-Martin N, Perez L, Payandeh J, Ciferri C Sci Adv. 2022 Mar 11;8(10):eabm2536. doi: 10.1126/sciadv.abm2536. Epub 2022 Mar , 11. PMID:35275719[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kschonsak M, Johnson MC, Schelling R, Green EM, Rougé L, Ho H, Patel N, Kilic C, Kraft E, Arthur CP, Rohou AL, Comps-Agrar L, Martinez-Martin N, Perez L, Payandeh J, Ciferri C. Structural basis for HCMV Pentamer receptor recognition and antibody neutralization. Sci Adv. 2022 Mar 11;8(10):eabm2536. PMID:35275719 doi:10.1126/sciadv.abm2536
