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    The pre-fusion structure of Herpes simplex virus glycoprotein B

    Vollmer, B. and Pražák, V. and Vasishtan, D. and Jefferys, E.E. and Hernandez-Duran, A. and Vallbracht, M. and Klupp, B. and Mettenleiter, T.C. and Backovic, M. and Rey, F.A. and Topf, Maya and Grünewald, K. (2020) The pre-fusion structure of Herpes simplex virus glycoprotein B. Science Advances 6 (39), ISSN 2375-2548.

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    Abstract

    Cell entry of enveloped viruses requires specialized viral proteins which 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 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the post-fusion form, thereby precluding structural elucidation of the pharmacologically relevant pre-fusion 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 pre-fusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a striking conservation of conformational domain rearrangements during fusion between HSV-1 gB and the Vesicular Stomatitis Virus glycoprotein G (VSV-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. Rey, M. Topf, K.

    Metadata

    Item Type: Article
    School: School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 02 Dec 2020 17:30
    Last Modified: 19 Jun 2021 13:41
    URI: https://eprints.bbk.ac.uk/id/eprint/40774

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