National Center for
4B3N: Crystal Structure Of Rhesus Trim5alpha Pry/spry Domain
Proc. Natl. Acad. Sci. U. S. A. (2012) 109 p.18372-18377
Tripartite motif protein isoform 5 alpha (TRIM5alpha) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5alpha recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5alpha induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5alpha PRY/SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5alpha PRY/SPRY, but not the human TRIM5alpha 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 TRIM5alpha that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5alpha-mediated retroviral restriction.