cpsf6 defines a conserved capsid interface that modulates hiv-1 replicationcpsf6定义了一个守恒的衣壳界面调节hiv - 1复制.pdfVIP

CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication 1. 2. 2¤ 1 3 Amanda J. Price , Adam J. Fletcher , Torsten Schaller , Tom Elliott , KyeongEun Lee , 3 1 2 1 Vineet N. KewalRamani , Jason W. Chin , Greg J. Towers , Leo C. James * 1 Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, United Kingdom, 2 Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom, 3 HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, United States of America Abstract 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 nucl