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

Citations Over TimeTop 10% of 2016 papers

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.

Related Papers

• → Potential role of cyclophilin A in regulating cytokine secretion(2017)82 cited
• → The use of AlphaLISA technology to detect interaction between hepatitis C virus-encoded NS5A and cyclophilin A(2010)43 cited
• → Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A(2019)26 cited
• → Catalysis and Binding of Cyclophilin A with Different HIV-1 Capsid Constructs(2004)40 cited
• → Mechanistic Independence of Nef and Cyclophilin A Enhancement of Human Immunodeficiency Virus Type 1 Infectivity(1998)27 cited