5FJB

Cyclophilin A Stabilize HIV-1 Capsid through a Novel Non- canonical Binding Site

Summary for 5FJB

• Entry DOI: 10.2210/pdb5fjb/pdb
• EMDB information: 3076
• Descriptor: GAG POLYPROTEIN, PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A (2 entities in total)
• Functional Keywords: isomerase
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1; More
• Cellular location: Gag polyprotein: Host cell membrane ; Lipid-anchor . Matrix protein p17: Virion membrane ; Lipid-anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion : P03347; Cytoplasm : P62937
• Total number of polymer chains: 3
• Total formula weight: 66597.13

Authors

Liu, C.,Perilla, J.R.,Ning, J.,Lu, M.,Hou, G.,Ramalhu, R.,Bedwell, G.J.,Ahn, J.,Shi, J.,Gronenborn, A.M.,Prevelige Jr, P.E.,Rousso, I.,Aiken, C.,Polenova, T.,Schulten, K.,Zhang, P. (deposition date: 2015-10-07, release date: 2016-03-16, Last modification date: 2024-10-23)

Primary citation

Liu, C.,Perilla, J.R.,Ning, J.,Lu, M.,Hou, G.,Ramalho, R.,Himes, B.A.,Zhao, G.,Bedwell, G.J.,Byeon, I.,Ahn, J.,Gronenborn, A.M.,Prevelige, P.E.,Rousso, I.,Aiken, C.,Polenova, T.,Schulten, K.,Zhang, P.
Cyclophilin a Stabilizes the HIV-1 Capsid Through a Novel Non-Canonical Binding Site.
Nat.Commun., 7:10714-, 2016

PubMed 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.

PubMed: 26940118
DOI: 10.1038/NCOMMS10714

Experimental method

ELECTRON MICROSCOPY (9 Å)