@article{3f3a26c2c5b84e55a2156fbf1d7fc71f,
title = "Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site",
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.",
author = "Chuang Liu and Perilla, {Juan R.} and Jiying Ning and Manman Lu and Guangjin Hou and Ruben Ramalho and Himes, {Benjamin A.} and Gongpu Zhao and Bedwell, {Gregory J.} and Byeon, {In Ja} and Jinwoo Ahn and Gronenborn, {Angela M.} and Prevelige, {Peter E.} and Itay Rousso and Christopher Aiken and Tatyana Polenova and Klaus Schulten and Peijun Zhang",
note = "Funding Information: We thank Dr Teresa Brosenitsch for critical reading of the manuscript. This work was supported by the National Institutes of Health NIGMS Grant R01GM085043 (P.Z.), P50GM082251 (A.M.G.), P41GM104601 (K.S.), R01GM067887 (K.S.), the National Science Foundation (NSF) PHY-1430124 (K.S.) and the Israeli Science Foundation (grant 1115/13) (I.R.). Large-scale MD simulations were performed on the Blue Waters supercomputer, financed by the NSF (awards OCI-0725070 and ACI-1238993), and on Titan Supercomputers, supported by the Department of Energy (Contract DE-AC05-00OR22725). T.P. acknowledges the support of the NSF CHE0959496 grant, for acquisition of an 850 MHz NMR spectrometer, and the NIGMS P30GM110758 grant for support of core instrumentation infrastructure at the University of Delaware.",
year = "2016",
month = jan,
day = "1",
doi = "10.1038/ncomms10714",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
