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The Role of RING Dimerization in the E3 Ubiquitin Ligase Activity of the TRIM5α Retroviral Restriction Factor
Author(s) -
Ivanov Dmitri,
Yudina Zinaida,
Johnson Rory,
Biris Nikolaos,
Taylor Alexander,
Hart P,
Demeler Borries
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.888.9
Subject(s) - ubiquitin ligase , capsid , dimer , ubiquitin , dna ligase , biology , cysteine , microbiology and biotechnology , chemistry , biochemistry , dna , gene , enzyme , organic chemistry
Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immunity responses by catalyzing synthesis of K63‐linked polyubiquitin chains in a manner that is dependent on either direct or indirect interaction with pathogen‐associated molecular patterns. In this study we investigate the mechanism, by which the TRIM5α retroviral restriction factor activates Ubc13, the K63‐linkage specific E2 Ub‐conjugating enzyme. 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. The two RING domains within the TRIM dimer are located on the opposite ends of the approximately 170 angstrom‐long rod‐shaped molecule, thus the RING dimer is most likely formed as the result of higher‐order oligomerization of TRIM5α promoted by the interaction with the retroviral capsid. The mechanism we describe, which links capsid‐mediated higher‐order assembly of TRIM5α with the RING‐mediated E3 Ub ligase activity, is likely to be conserved in many other members of TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection.