RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin

Zinaida Yudina, Amanda Roa, Rory Johnson, Nikolaos Biris, Daniel A. de Souza Aranha Vieira, Vladislav Tsiperson, Natalia Reszka, Alexander B. Taylor, P. John Hart, Borries Demeler, Felipe Diaz-Griffero, Dmitri N. Ivanov

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41 Scopus citations

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 TRIM5α retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5α:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5α RING domain. Our data explain how higher-order oligomerization of TRIM5α, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5α 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.

Original languageEnglish (US)
Pages (from-to)788-797
Number of pages10
JournalCell Reports
Volume12
Issue number5
DOIs
StatePublished - Aug 4 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yudina, Z., Roa, A., Johnson, R., Biris, N., de Souza Aranha Vieira, D. A., Tsiperson, V., Reszka, N., Taylor, A. B., Hart, P. J., Demeler, B., Diaz-Griffero, F., & Ivanov, D. N. (2015). RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin. Cell Reports, 12(5), 788-797. https://doi.org/10.1016/j.celrep.2015.06.072