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

Academic Article

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.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 8963352
  • Author List

  • Liu C; Perilla JR; Ning J; Lu M; Hou G; Ramalho R; Himes BA; Zhao G; Bedwell GJ; Byeon IJ
  • Volume

  • 7