The RING domain of TRIM69 promotes higher‐order assembly

Members of the TRIM protein family have been shown to inhibit a range of viral infections. Recently, TRIM69 was identified as a potent inhibitor of Vesicular stomatitis Indiana virus infection, with its inhibition being dependent upon multimerization. Using SEC‐MALLS analysis, it is demonstrated that the assembly of TRIM69 is mediated through the RING domain and not the Bbox domain as has been shown for other TRIM proteins. Using X‐ray crystallography, the structure of the TRIM69 RING domain has been determined to a resolution of 2.1 Å, the oligomerization interface has been identified and regions outside the four‐helix bundle have been observed to form interactions that are likely to support assembly. TRIM‐protein RING domains commonly exist in a weak monomer–dimer association; here, it is shown that the RING domain of TRIM69 forms a tight dimer and the structure is used to discuss the reasons for this high‐affinity interaction.