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

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. Prevelige, Itay Rousso, Christopher Aiken, Tatyana Polenova, Klaus Schulten, Peijun Zhang

Research output: Contribution to journalArticlepeer-review

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-A 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.

Original languageEnglish (US)
Article number10714
JournalNature communications
Volume7
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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