Journal
CELL REPORTS
Volume 12, Issue 5, Pages 788-797Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.06.072
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Funding
- Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) [NIH P50 GM082545]
- Robert A. Welch Foundation [AQ-1399]
- NIH [R01 AI087390, R21 AI102824, R56 AI108432, R01 AI104476, P30 CA054174]
- Cancer Prevention and Research Institute of Texas (CPRIT)
- NIH-NIGMS [P41 GM103403]
- NIH-ORIP HEI at Argonne National Laboratory under DOE Office of Science [S10 RR029205, DE-AC02-06CH11357]
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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 alpha retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5 alpha: Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5 alpha RING domain. Our data explain how higher-order oligomerization of TRIM5 alpha, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5 alpha 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.
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