A pocket-factor–triggered conformational switch in the hepatitis B virus capsid
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2021-04-27
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Journal Article
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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.
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published
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118 (17)
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National Academy of Sciences
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Subject
hepatitis B virus; solid-state NMR; hydrophobic pocket; Triton
Organisational unit
03496 - Meier, Beat H. (emeritus) / Meier, Beat H. (emeritus)