Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery.

Autor: Vaney MC; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France., Dellarole M; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.; CIBION, CONICET, Buenos Aires, Argentina., Duquerroy S; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.; Université Paris Saclay, Faculté des Sciences, Orsay, France., Medits I; Center for Virology, Medical University of Vienna, Vienna, Austria., Tsouchnikas G; Center for Virology, Medical University of Vienna, Vienna, Austria.; HOOKIPA Pharma 19 Inc, Vienna, Austria., Rouvinski A; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.; Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel., England P; Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Plateforme de Biophysique Moléculaire, Paris, France., Stiasny K; Center for Virology, Medical University of Vienna, Vienna, Austria. karin.stiasny@meduniwien.ac.at., Heinz FX; Center for Virology, Medical University of Vienna, Vienna, Austria. Franz.X.Heinz@meduniwien.ac.at., Rey FA; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France. felix.rey@pasteur.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 28; Vol. 13 (1), pp. 3718. Date of Electronic Publication: 2022 Jun 28.
DOI: 10.1038/s41467-022-31111-y
Abstrakt: The flavivirus envelope glycoproteins prM and E drive the assembly of icosahedral, spiky immature particles that bud across the membrane of the endoplasmic reticulum. Maturation into infectious virions in the trans-Golgi network involves an acid-pH-driven rearrangement into smooth particles made of (prM/E) 2 dimers exposing a furin site for prM cleavage into "pr" and "M". Here we show that the prM "pr" moiety derives from an HSP40 cellular chaperonin. Furthermore, the X-ray structure of the tick-borne encephalitis virus (pr/E) 2 dimer at acidic pH reveals the E 150-loop as a hinged-lid that opens at low pH to expose a positively-charged pr-binding pocket at the E dimer interface, inducing (prM/E) 2 dimer formation to generate smooth particles in the Golgi. Furin cleavage is followed by lid-closure upon deprotonation in the neutral-pH extracellular environment, expelling pr while the 150-loop takes the relay in fusion loop protection, thus revealing the elusive flavivirus mechanism of fusion activation.
(© 2022. The Author(s).)
Databáze: MEDLINE
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