Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site
Date
2016-03-04
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Nature Publishing Group
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.
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Citation
Liu, 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).