Authors: 
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
Journal: 
Nature Communications
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.
Date: 
2016
Number: 
7
Pages: 
10714
keywords: 
Virology
Biophysics
Computational Modeling
Structural Biology