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The prefusion structure of herpes simplex virus glycoprotein B

Abstract : Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins.
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Submitted on : Monday, June 14, 2021 - 2:11:06 PM
Last modification on : Tuesday, June 15, 2021 - 11:33:50 AM
Long-term archiving on: : Thursday, September 16, 2021 - 8:22:17 AM

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B. Vollmer, V. Pražák, D. Vasishtan, E. Jefferys, A. Hernandez-Duran, et al.. The prefusion structure of herpes simplex virus glycoprotein B. Science Advances , American Association for the Advancement of Science (AAAS), 2020, 6 (39), pp.eabc1726. ⟨10.1126/sciadv.abc1726⟩. ⟨pasteur-03259717⟩

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