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
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Proceedings of the National Academy of Sciences of the United States of America. - 118, 17 (2021) , e2022464118, ISSN: 1091-6490
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
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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
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10.1073/pnas.2022464118
- URN
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urn:nbn:de:bsz:25-freidok-2187854
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:43 MEZ
Datenpartner
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Beteiligte
- 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
- Universität
Entstanden
- 2023