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

Author

Listed:
  • Chuang Liu

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Juan R. Perilla

    (University of Illinois at Urbana-Champaign)

  • Jiying Ning

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Manman Lu

    (Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine
    University of Delaware)

  • Guangjin Hou

    (Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine
    University of Delaware)

  • Ruben Ramalho

    (Ben-Gurion University of the Negev)

  • Benjamin A. Himes

    (University of Pittsburgh School of Medicine)

  • Gongpu Zhao

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Gregory J. Bedwell

    (University of Alabama at Birmingham)

  • In-Ja Byeon

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Jinwoo Ahn

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Angela M. Gronenborn

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

  • Peter E. Prevelige

    (Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine
    University of Alabama at Birmingham)

  • Itay Rousso

    (Ben-Gurion University of the Negev)

  • Christopher Aiken

    (Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine
    Microbiology and Immunology, Vanderbilt University School of Medicine)

  • Tatyana Polenova

    (Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine
    University of Delaware)

  • Klaus Schulten

    (University of Illinois at Urbana-Champaign)

  • Peijun Zhang

    (University of Pittsburgh School of Medicine
    Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine)

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.

Suggested Citation

  • Chuang Liu & Juan R. Perilla & Jiying Ning & Manman Lu & Guangjin Hou & Ruben Ramalho & Benjamin A. Himes & Gongpu Zhao & Gregory J. Bedwell & In-Ja Byeon & Jinwoo Ahn & Angela M. Gronenborn & Peter E, 2016. "Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10714
    DOI: 10.1038/ncomms10714
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