Tripartite motif protein isoform 5 alpha (TRIM5α) is a potent antiviral protein 
that restricts infection by HIV-1 and other retroviruses. TRIM5α recognizes the 
lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a 
species-specific manner. Upon binding, TRIM5α induces premature disassembly of 
the viral capsid and activates the downstream innate immune response. We have 
determined the crystal structure of the rhesus TRIM5α PRY/SPRY domain that 
reveals essential features for capsid binding. Combined cryo-electron microscopy 
and biochemical data show that the monomeric rhesus TRIM5α PRY/SPRY, but not the 
human TRIM5α 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 TRIM5α that is capable of 
interacting with viral capsids of different curvatures. Our results provide 
molecular insights into the mechanisms of TRIM5α-mediated retroviral 
restriction.