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) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRalpha) and transforming growth factor beta receptor 3 (TGFbetaR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRalpha and TGFbetaR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRalpha and TGFbetaR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRalpha interaction has an inhibitory effect on PDGFRalpha signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV.
Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry.,Kschonsak M, Rouge L, Arthur CP, Hoangdung H, Patel N, Kim I, Johnson MC, Kraft E, Rohou AL, Gill A, Martinez-Martin N, Payandeh J, Ciferri C Cell. 2021 Mar 4;184(5):1232-1244.e16. doi: 10.1016/j.cell.2021.01.036. Epub 2021, Feb 23. PMID:33626330[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kschonsak M, Rouge L, Arthur CP, Hoangdung H, Patel N, Kim I, Johnson MC, Kraft E, Rohou AL, Gill A, Martinez-Martin N, Payandeh J, Ciferri C. Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry. Cell. 2021 Mar 4;184(5):1232-1244.e16. doi: 10.1016/j.cell.2021.01.036. Epub 2021, Feb 23. PMID:33626330 doi:http://dx.doi.org/10.1016/j.cell.2021.01.036
