Liu, ChuangPerilla, Juan R.Ning, JiyingLu, ManmanHou, GuangjinRamalho, RubenHimes, Benjamin A.Zhao, GongpuBedwell, Gregory J.Byeon, In-JaAhn, JinwooGronenborn, Angela M.Prevelige, Peter E.Rousso, ItayAiken, ChristopherPolenova, TatyanaSchulten, KlausZhang, Peijun2016-11-042016-11-04Copyright2016-03-04Liu, C. et al. Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site. Nat. Commun. 7:10714 doi: 10.1038/ncomms10714 (2016).2041-1723http://udspace.udel.edu/handle/19716/19829Publisher's PDFThe 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.en-USCC BY 4.0ArticleDOI: 10.1038/ncomms10714