Crystal structure of an HIV assembly and maturation switch

Wagner, Jonathan M.; Zadrozny, Kaneil K.; Chrustowicz, Jakub; Purdy, Michael D.; Yeager, Mark; Ganser-Pornillos, Barbie K.; Pornillos, Owen

doi:10.7554/eLife.17063

Title: Crystal structure of an HIV assembly and maturation switch

Journal Article · Thu Jul 14 00:00:00 EDT 2016 · eLife

DOI:https://doi.org/10.7554/eLife.17063· OSTI ID:1267471

Wagner, Jonathan M. ^[1]; Zadrozny, Kaneil K. ^[1]; Chrustowicz, Jakub ^[1]; Purdy, Michael D. ^[1]; Yeager, Mark ^[2]; Ganser-Pornillos, Barbie K. ^[1];

^[1]

Univ. of Virginia, Charlottesville, VA (United States)
Univ. of Virginia, Charlottesville, VA (United States); Univ. of Virginia Health System, Charlottesville, VA (United States)

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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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health

Grant/Contract Number:: R01-GM066087; P50-GM082545; P50-GM103297; F32-GM115007; S10-RR025067

OSTI ID:: 1267471

Journal Information:: eLife, Vol. 5, Issue 2016; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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