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. Author manuscript; available in PMC: 2021 Nov 3.
Published in final edited form as: Nat Struct Mol Biol. 2021 Feb 25;28(3):278–289. doi: 10.1038/s41594-021-00560-2

Fig. 7. Model for target-induced clustering mechanism and its applications.

Fig. 7

The two RING domains of the TRIM21 dimer are held apart by an elongated antiparallel coiled-coil. Target-induced clustering allows intermolecular RING dimerisation, which facilitates E2~Ub binding and catalysis of K63-linked ubiquitin chains on TRIM21 leading to proteasomal degradation of TRIM21 and its targets. TRIM21 clustering can be induced by antibody-coated virus, internalised immune complexes or proteins targeted with antibodies. This mechanism has therapeutic potential for selective degradation of repeat-epitope or aggregated disease proteins (orange shaded area). New protein depletion tools based on the sufficiency of molecular clustering and RING dimerisation for TRIM21-mediated degradation (green shaded area).