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Crystal structure of an HIV assembly and maturation switch.

ABSTRACT: Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II ?-turn, and the stem comprises a 6-helix bundle. The ?-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysis during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.

SUBMITTER: Wagner JM

PROVIDER: S-EPMC4946879 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Crystal structure of an HIV assembly and maturation switch.

Wagner Jonathan M JM Zadrozny Kaneil K KK Chrustowicz Jakub J Purdy Michael D MD Yeager Mark M Ganser-Pornillos Barbie K BK Pornillos Owen O

eLife 20160714

Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an e ...[more]

PMID: 27416583

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