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Crystal structure of an HIV assembly and maturation switch.

Crystal structure of an HIV assembly and maturation switch.
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Wagner JM, Zadrozny KK, Chrustowicz J, Purdy MD, Yeager M, Ganser-Pornillos BK, Pornillos O,


Wagner JM, Zadrozny KK, Chrustowicz J, Purdy MD, Yeager M, Ganser-Pornillos BK, Pornillos O, (click to view)

Wagner JM, Zadrozny KK, Chrustowicz J, Purdy MD, Yeager M, Ganser-Pornillos BK, Pornillos O,

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eLife 2016 07 145() doi 10.7554/eLife.17063

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 β-turn, and the stem comprises a 6-helix bundle. The β-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.

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