DOI: 10.1038/ncomms10714. Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site

Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site

10.1038/ncomms10714

Crossref journal-article

Springer Science and Business Media LLC

Nature Communications (297)

Abstract

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 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.

Bibliography

Liu, C., Perilla, J. R., Ning, J., Lu, M., Hou, G., Ramalho, R., Himes, B. A., Zhao, G., Bedwell, G. J., Byeon, I.-J., Ahn, J., Gronenborn, A. M., Prevelige, P. E., Rousso, I., Aiken, C., Polenova, T., Schulten, K., & Zhang, P. (2016). Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site. Nature Communications, 7(1).

Authors 18

Chuang Liu (first)
Juan R. Perilla (additional)
Jiying Ning (additional)
Manman Lu (additional)
Guangjin Hou (additional)
Ruben Ramalho (additional)
Benjamin A. Himes (additional)
Gongpu Zhao (additional)
Gregory J. Bedwell (additional)
In-Ja Byeon (additional)
Jinwoo Ahn (additional)
Angela M. Gronenborn (additional)
Peter E. Prevelige (additional)
Itay Rousso (additional)
Christopher Aiken (additional)
Tatyana Polenova (additional)
Klaus Schulten (additional)
Peijun Zhang (additional)

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Dates

Type	When
Created	9 years, 5 months ago (March 4, 2016, 6:41 a.m.)
Deposited	2 years, 7 months ago (Jan. 4, 2023, 6:35 a.m.)
Indexed	3 weeks ago (Aug. 2, 2025, 12:56 a.m.)
Issued	9 years, 5 months ago (March 4, 2016)
Published	9 years, 5 months ago (March 4, 2016)
Published Online	9 years, 5 months ago (March 4, 2016)

Funders 0

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BibTeX

@article{Liu_2016, title={Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site}, volume={7}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/ncomms10714}, DOI={10.1038/ncomms10714}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Liu, Chuang and Perilla, Juan R. and Ning, Jiying and Lu, Manman and Hou, Guangjin and Ramalho, Ruben and Himes, Benjamin A. and Zhao, Gongpu and Bedwell, Gregory J. and Byeon, In-Ja and Ahn, Jinwoo and Gronenborn, Angela M. and Prevelige, Peter E. and Rousso, Itay and Aiken, Christopher and Polenova, Tatyana and Schulten, Klaus and Zhang, Peijun}, year={2016}, month=mar }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>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-\u00c5 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.</jats:p>",
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