National Center for
5EIU: Mini TRIM5 B-box 2 dimer C2 crystal form
Mechanism of B-box 2 domain-mediated higher-order assembly of the retroviral restriction factor TRIM5alpha
Elife (2016) 5
Restriction factors and pattern recognition receptors are important components of intrinsic cellular defenses against viral infection. Mammalian TRIM5alpha proteins are restriction factors and receptors that target the capsid cores of retroviruses and activate ubiquitin-dependent antiviral responses upon capsid recognition. Here, we report crystallographic and functional studies of the TRIM5alpha B-box 2 domain, which mediates higher-order assembly of TRIM5 proteins. The B-box can form both dimers and trimers, and the trimers can link multiple TRIM5alpha proteins into a hexagonal net that matches the lattice arrangement of capsid subunits and enables avid capsid binding. Two modes of conformational flexibility allow TRIM5alpha to accommodate the variable curvature of retroviral capsids. B-box mediated interactions also modulate TRIM5alpha's E3 ubiquitin ligase activity, by stereochemically restricting how the N-terminal RING domain can dimerize. Overall, these studies define important molecular details of cellular recognition of retroviruses, and how recognition links to downstream processes to disable the virus.