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Identification of RING E3 pseudoligases in the TRIM protein family

Author

Listed:
  • Jane Dudley-Fraser

    (The Francis Crick Institute)

  • Diego Esposito

    (The Francis Crick Institute)

  • Katherine A. McPhie

    (The Francis Crick Institute)

  • Coltrane Morley-Williams

    (The Francis Crick Institute)

  • Tania Auchynnikava

    (The Francis Crick Institute)

  • Katrin Rittinger

    (The Francis Crick Institute)

Abstract

TRIpartite Motif (TRIM) family proteins have diverse roles across a broad variety of cellular functions, which are largely presumed to depend on their ubiquitin E3 ligase activity, conferred by a RING domain. However, recent reports have shown that some TRIMs lack detectable ubiquitination activity in isolation, despite containing a RING domain. Here, we present parallel in cellulo, in vitro, and in silico structure-function analyses of the ubiquitin E3 ligase activity and RING domain structural characteristics of the whole TRIM protein family. In-depth follow-up studies of this comprehensive dataset reveals a number of ‘pseudoligases’, whose RING domains have structurally diverged at either the homodimerisation or E2~ubiquitin interfaces, thereby disrupting their ability to catalyse ubiquitin transfer. Together, these data raise intriguing open questions regarding the unknown TRIM functions in physiology and disease.

Suggested Citation

  • Jane Dudley-Fraser & Diego Esposito & Katherine A. McPhie & Coltrane Morley-Williams & Tania Auchynnikava & Katrin Rittinger, 2025. "Identification of RING E3 pseudoligases in the TRIM protein family," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58807-1
    DOI: 10.1038/s41467-025-58807-1
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