Structural insight into HIV-1 capsid recognition by rhesus TRIM5?.

ABSTRACT: Tripartite motif protein isoform 5 alpha (TRIM5?) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5? recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5? induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5? PRY/SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5? PRY/SPRY, but not the human TRIM5? PRY/SPRY, can bind to HIV-1 capsid protein assemblies without causing disruption of the capsid. This suggests that the PRY/SPRY domain alone constitutes an important pattern-sensing component of TRIM5? that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5?-mediated retroviral restriction.

SUBMITTER: Yang H 

PROVIDER: S-EPMC3494900 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature