5fz2 | pdb_00005fz2
Natively membrane-anchored full-length Herpes simplex virus 1 glycoprotein B
Structural highlights
Function[GB_HHV1K] Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moities of the host cell surface proteoglycans. Involved in fusion of viral and cellular membranes leading to virus entry into the host cell. Following initial binding of gD to one of its receptors, membrane fusion is mediated by the fusion machinery composed at least 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 egress. Also plays a role, together with gK, in virus-induced cell-to-cell fusion (syncytia formation).[1] Publication Abstract from PubMedMany viruses are enveloped by a lipid bilayer acquired during assembly, which is typically studded with one or two types of glycoproteins. These viral surface proteins act as the primary interface between the virus and the host. Entry of enveloped viruses relies on specialized fusogen proteins to help merge the virus membrane with the host membrane. In the multicomponent herpesvirus fusion machinery, glycoprotein B (gB) acts as this fusogen. Although the structure of the gB ectodomain postfusion conformation has been determined, any other conformations (e.g., prefusion, intermediate conformations) have so far remained elusive, thus restricting efforts to develop antiviral treatments and prophylactic vaccines. Here, we have characterized the full-length herpes simplex virus 1 gB in a native membrane by displaying it on cell-derived vesicles and using electron cryotomography. Alongside the known postfusion conformation, a novel one was identified. Its structure, in the context of the membrane, was determined by subvolume averaging and found to be trimeric like the postfusion conformation, but appeared more condensed. Hierarchical constrained density-fitting of domains unexpectedly revealed the fusion loops in this conformation to be apart and pointing away from the anchoring membrane. This vital observation is a substantial step forward in understanding the complex herpesvirus fusion mechanism, and opens up new opportunities for more targeted intervention of herpesvirus entry. Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B.,Zeev-Ben-Mordehai T, Vasishtan D, Hernandez Duran A, Vollmer B, White P, Prasad Pandurangan A, Siebert CA, Topf M, Grunewald K Proc Natl Acad Sci U S A. 2016 Mar 24. pii: 201523234. PMID:27035968[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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