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Nat Commun. 2016 Mar 4;7:10714. doi: 10.1038/ncomms10714.

Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site.

Author information

1
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
2
Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
3
Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
4
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
5
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Be'er-Sheva, 84105, Israel.
6
Department of Microbiology, University of Alabama at Birmingham, Birmingham Alabama 35294, USA.
7
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Abstract

The host cell factor cyclophilin A (CypA) interacts directly with the HIV-1 capsid and regulates viral infectivity. Although the crystal structure of CypA in complex with the N-terminal domain of the HIV-1 capsid protein (CA) has been known for nearly two decades, how CypA interacts with the viral capsid and modulates HIV-1 infectivity remains unclear. We determined the cryoEM structure of CypA in complex with the assembled HIV-1 capsid at 8-Å resolution. The structure exhibits a distinct CypA-binding pattern in which CypA selectively bridges the two CA hexamers along the direction of highest curvature. EM-guided all-atom molecular dynamics simulations and solid-state NMR further reveal that the CypA-binding pattern is achieved by single-CypA molecules simultaneously interacting with two CA subunits, in different hexamers, through a previously uncharacterized non-canonical interface. These results provide new insights into how CypA stabilizes the HIV-1 capsid and is recruited to facilitate HIV-1 infection.

PMID:
26940118
PMCID:
PMC4785225
DOI:
10.1038/ncomms10714
[Indexed for MEDLINE]
Free PMC Article

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