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TitleCyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site.
Journal, issue, pagesNat Commun, Vol. 7, Page 10714, Year 2016
Publish dateMar 4, 2016
AuthorsChuang 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 /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:26940118 / PubMed Central
MethodsEM (helical sym.)
Resolution8.0 - 9 Å
Structure data

EMDB-3075:
Cyclophilin A Stabilizes HIV-1 Capsid through a Novel Non-canonical Binding Site
Method: EM (helical sym.) / Resolution: 8.0 Å

3076

5fjb

EMDB-3076: Cyclophilin A Stabilize HIV-1 Capsid through a Novel Non-canonical Binding Site
PDB-5fjb: Cyclophilin A Stabilize HIV-1 Capsid through a Novel Non- canonical Binding Site
Method: EM (helical sym.) / Resolution: 8.0 Å

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsISOMERASE

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