A pocket-factor–triggered conformational switch in the hepatitis B virus capsid

Abstract: Viral hepatitis is growing into an epidemic illness, and it is urgent to neutralize the main culprit, hepatitis B virus (HBV), a small-enveloped retrotranscribing DNA virus. An intriguing observation in HB virion morphogenesis is that capsids with immature genomes are rarely enveloped and secreted. This prompted, in 1982, the postulate that a regulated conformation switch in the capsid triggers envelopment. Using solid-state NMR, we identified a stable alternative conformation of the capsid. The structural variations focus on the hydrophobic pocket of the core protein, a hot spot in capsid–envelope interactions. This structural switch is triggered by specific, high-affinity binding of a pocket factor. The conformational change induced by the binding is reminiscent of a maturation signal. This leads us to formulate the “synergistic double interaction” hypothesis, which explains the regulation of capsid envelopment and indicates a concept for therapeutic interference with HBV envelopment

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Proceedings of the National Academy of Sciences of the United States of America. - 118, 17 (2021) , e2022464118, ISSN: 1091-6490

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2023
Urheber
Lecoq, Lauriane
Wang, Shishan
Dujardin, Marie
Zimmermann, Peter
Schuster, Leonard
Fogeron, Marie-Laure
Briday, Mathilde
Schledorn, Maarten
Wiegand, Thomas
Cole, Laura
Montserret, Roland
Bressanelli, Stéphane
Meier, Beat H.
Nassal, Michael
Böckmann, Anja

DOI
10.1073/pnas.2022464118
URN
urn:nbn:de:bsz:25-freidok-2187854
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:43 MEZ

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