Publication Abstract from PubMed
The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.
CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication.,Price AJ, Fletcher AJ, Schaller T, Elliott T, Lee K, Kewalramani VN, Chin JW, Towers GJ, James LC PLoS Pathog. 2012 Aug;8(8):e1002896. Epub 2012 Aug 30. PMID:22956906[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
