Crystal structure of an HIV assembly and maturation switch

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Abstract

Virus assembly and maturation proceeds 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 prevent unfolding of the CA-SP1 junction and thereby deny access of the viral protease to its substrate.

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Jonathan M Wagner

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

Competing interests
The authors declare that no competing interests exist.
Kaneil K Zadrozny

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

Competing interests
The authors declare that no competing interests exist.
Jakub Chrustowicz

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

Competing interests
The authors declare that no competing interests exist.
Michael D Purdy

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

Competing interests
The authors declare that no competing interests exist.
Mark Yeager

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

For correspondence
my3r@virginia.edu

Competing interests
The authors declare that no competing interests exist.
Barbie K Ganser-Pornillos

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

For correspondence
bpornillos@virginia.edu

Competing interests
The authors declare that no competing interests exist.
Owen Pornillos

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

For correspondence
owp3a@eservices.virginia.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9056-5002

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