5v2s
From Proteopedia
Crystal structure of glycoprotein B from Herpes Simplex Virus type I
Structural highlights
FunctionGB_HHV11 Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moieties 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 to its host receptors, membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. May be involved in the fusion between the virion envelope and the outer nuclear membrane during virion egress (By similarity). Also plays a role, together with gK, in virus-induced cell-to-cell fusion (syncytia formation).[HAMAP-Rule:MF_04032][1] Publication Abstract from PubMedViral fusogens merge viral and cell membranes during cell penetration. Their ectodomains drive fusion by undergoing large-scale refolding, but little is known about the functionally important regions located within or near the membrane. Here we report the crystal structure of full-length glycoprotein B (gB), the fusogen from herpes simplex virus, complemented by electron spin resonance measurements. The membrane-proximal (MPR), transmembrane (TMD), and cytoplasmic (CTD) domains form a uniquely folded trimeric pedestal beneath the ectodomain, which balances dynamic flexibility with extensive, stabilizing membrane interactions. The postfusion conformation of the ectodomain suggests that the CTD likewise adopted the postfusion form. However, hyperfusogenic mutations, which destabilize the prefusion state of gB, target key interfaces and structural motifs that reinforce the observed CTD structure. Thus, a similar CTD structure must stabilize gB in its prefusion state. Our data suggest a model for how this dynamic, membrane-dependent 'clamp' controls the fusogenic refolding of gB. Structural basis for membrane anchoring and fusion regulation of the herpes simplex virus fusogen gB.,Cooper RS, Georgieva ER, Borbat PP, Freed JH, Heldwein EE Nat Struct Mol Biol. 2018 May;25(5):416-424. doi: 10.1038/s41594-018-0060-6. Epub, 2018 May 4. PMID:29728654[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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