Exploration of the TRIM fold of MuRF1 using EPR reveals a canonical antiparallel structure and extended COS-box

Michael Stevens, Barbara Franke, Katarzyna A. Skorupka, David S. Cafiso, Owen Pornillos, Olga Mayans, David G. Norman (Lead / Corresponding author)

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3 Citations (Scopus)
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Abstract

MuRF1 (TRIM63) is a RING-type E3 ubiquitin ligase with a predicted tripartite TRIM fold. TRIM proteins rely upon the correct placement of an N-terminal RING domain, with respect to C-terminal, specific substrate-binding domains. The TRIM domain organization is orchestrated by a central helical domain that forms an antiparallel coiled-coil motif and mediates the dimerization of the fold. MuRF1 has a reduced TRIM composition characterized by a lack of specific substrate binding domains, but contains in its helical domain a conserved sequence motif termed COS-box that has been speculated to fold independently into an α-hairpin. These characteristics had led to question whether MuRF1 adopts a canonical TRIM fold. Using a combination of electron paramagnetic resonance, on spin-labeled protein, and disulfide crosslinking, we show that TRIM63 follows the structural conservation of the TRIM dimerization domain, observed in other proteins. We also show that the COS-box motif folds back onto the dimerization coiled-coil motif, predictably forming a four-helical bundle at the center of the protein and emulating the architecture of canonical TRIMs.

Original languageEnglish
Pages (from-to)2900-2909
Number of pages10
JournalJournal of Molecular Biology
Volume431
Issue number15
Early online date22 May 2019
DOIs
Publication statusPublished - 12 Jul 2019

Keywords

  • MuRF1
  • PELDOR
  • TRIM fold
  • coiled-coil
  • disulfide cross-linking

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