Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity

EMBO J. 2016 Jun 1;35(11):1204-18. doi: 10.15252/embj.201593741. Epub 2016 May 6.


TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function.

Keywords: TRIM25; TRIM32; enzyme mechanism; protein structure; ubiquitin ligase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization
  • Humans
  • Protein Conformation
  • Protein Multimerization
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*
  • Tripartite Motif Proteins / chemistry*
  • Tripartite Motif Proteins / metabolism*
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination


  • Transcription Factors
  • Tripartite Motif Proteins
  • TRIM25 protein, human
  • TRIM32 protein, human
  • Ubiquitin-Protein Ligases