RING Dimerization Links Higher-Order Assembly of TRIM5? to Synthesis of K63-Linked Polyubiquitin.

ABSTRACT: Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5? retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5?:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5? RING domain. Our data explain how higher-order oligomerization of TRIM5?, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5? and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection.

SUBMITTER: Yudina Z 

PROVIDER: S-EPMC4526822 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature