Schematic diagram showing current models of TRIM5-mediated restriction. Free TRIM5 probably exists as a dimer in the target cell cytoplasm. Upon interaction with the capsid of a restriction-sensitive retrovirus, the propensity of TRIM5 to form a complementary hexameric lattice is stimulated. This increases its intrinsic E3 ubiquitin ligase activity. If avidity for the retrovirus capsid is sufficient, the virion core prematurely uncoats and reverse transcription is blocked. Depending upon the proximity of particular cellular E2 enzymes, TRIM5 will either autoubiquitinate and traffic towards proteasomes, or it will activate the TAK1 kinase and downstream signaling molecules.
