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Elife. 2016 Jul 14;5. pii: e17063. doi: 10.7554/eLife.17063.

Crystal structure of an HIV assembly and maturation switch.

Author information

1
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
2
Department of Medicine, Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville, United States.

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.

KEYWORDS:

HIV; assembly; biochemistry; biophysics; capsid; structural biology

PMID:
27416583
PMCID:
PMC4946879
DOI:
10.7554/eLife.17063
[Indexed for MEDLINE]
Free PMC Article

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