Dataset Information

Importin ? Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes.

ABSTRACT: Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Mature cores are transported to the nucleus by a complex that includes both importin ? and importin ? (Imp? and Imp?), which bind to the core protein's C-terminal domains (CTDs). Here we have investigated the interactions of HBV core protein with importins in vitro. Strikingly, empty capsids and free core protein can bind Imp? without Imp?. Cryo-EM image reconstructions show that the CTDs, which are located inside the capsid, can extrude through the capsid to be bound by Imp?. Imp? density localized on the capsid exterior near the quasi-sixfold vertices, suggested a maximum of 30 Imp? per capsid. However, examination of complexes using single molecule charge-detection mass spectrometry indicate that some complexes include over 90 Imp? molecules. Cryo-EM of capsids incubated with excess Imp? shows a population of damaged particles and a population of "dark" particles with internal density, suggesting that Imp? is effectively swallowed by the capsids, which implies that the capsids transiently open and close and can be destabilized by Imp?. Though the in vitro complexes with great excess of Imp? are not biological, these results have implications for trafficking of empty capsids and free core protein; activities that affect the basis of chronic HBV infection.

SUBMITTER: Chen C

PROVIDER: S-EPMC4982637 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Importin β Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes.

Chen Chao C Wang Joseph Che-Yen JC Pierson Elizabeth E EE Keifer David Z DZ Delaleau Mildred M Gallucci Lara L Cazenave Christian C Kann Michael M Jarrold Martin F MF Zlotnick Adam A

PLoS pathogens 20160812 8

Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Mature cores are transported to the nucleus by a complex that includes both importin α and importin β (Impα and Impβ), which bind to the core protein's C-terminal domains (CTDs). Here we ...[more]

PMID: 27518410

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