4B4N

CPSF6 defines a conserved capsid interface that modulates HIV-1 replication

Summary for 4B4N

• Entry DOI: 10.2210/pdb4b4n/pdb
• Descriptor: GAG PROTEIN, CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR SUBUNIT 6 (3 entities in total)
• Functional Keywords: viral protein-rna binding protein complex, hiv-1, cyclophilin, viral protein/rna binding protein
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1; More
• Total number of polymer chains: 2
• Total formula weight: 17755.37

Authors

Price, A.J.,James, L.C. (deposition date: 2012-07-31, release date: 2012-09-19, Last modification date: 2023-12-20)

Primary citation

Price, A.J.,Fletcher, A.J.,Schaller, T.,Elliott, T.,Lee, K.,Kewalramani, V.N.,Chin, J.W.,Towers, G.J.,James, L.C.
Cpsf6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication.
Plos Pathog., 8:2896-, 2012

PubMed 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 nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.

PubMed: 22956906
DOI: 10.1371/JOURNAL.PPAT.1002896

Experimental method

X-RAY DIFFRACTION (1.813 Å)