Journal Article PUBDB-2024-05679

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The prefusion structure of herpes simplex virus glycoprotein B

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2020
Assoc. Washington, DC [u.a.]

Science advances 6(39), eabc1726 () [10.1126/sciadv.abc1726]
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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.

Classification:

Contributing Institute(s):
  1. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) - Kay Grünewald (CSSB-LIV-KG)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)
  2. DFG project 390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)
Experiment(s):
  1. No specific instrument

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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record
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 Record created 2024-08-30, last modified 2025-09-29


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