Solution NMR structure of the TRIM21 B-box2 and identification of residues involved in its interaction with the RING domain

PLoS One. 2017 Jul 28;12(7):e0181551. doi: 10.1371/journal.pone.0181551. eCollection 2017.


Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein ligase implicated in innate immune signaling by acting as an autoantigen and by modifying interferon regulatory factors. Here we report the three-dimensional solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21 residues 86-130, consists of a short α-helical segment with an N-terminal short β-strand and two anti-parallel β-strands jointly found the core, and adopts a RING-like fold. This ββαβ core largely defines the overall fold of the TRIM21 B-box2 and the coordination of one Zn2+ ion stabilizes the tertiary structure of the protein. Using NMR titration experiments, we have identified an exposed interaction surface, a novel interaction patch where the B-box2 is likely to bind the N-terminal RING domain. Our structure together with comparisons with other TRIM B-box domains jointly reveal how its different surfaces are employed for various modular interactions, and provides extended understanding of how this domain relates to flanking domains in TRIM proteins.

MeSH terms

  • Computational Biology
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Theoretical
  • Protein Binding
  • Tripartite Motif Proteins / chemistry*
  • Tripartite Motif Proteins / metabolism*


  • Tripartite Motif Proteins

Grants and funding

This project was supported by the Swedish Science Council (BW, MS), the Swedish Cancer Foundation (MS) and the Swedish Foundation for International Cooperation in Research and Higher Education (BW, MS).