Solution structure of MUL1-RING domain and its interaction with p53 transactivation domain.
Mitochondrial E3 ubiquitin ligase 1 (MUL1) is a multifunctional mitochondrial protein involved in various biological processes such as mitochondrial dynamics, cell growth, apoptosis, and mitophagy. MUL1 mediates the ubiquitylation of mitochondrial p53 for proteasomal degradation. Although the interaction of MUL1-RING domain with its substrate, p53, is a unique mechanism in ... RING-mediated ubiquitylation, the molecular basis of this process remains unknown. In this study, we determined the solution structure of the MUL1-RING domain and characterized its interaction with the p53 transactivation domain (p53-TAD) by nuclear magnetic resonance (NMR) spectroscopy. The overall structure of the MUL1-RING domain is similar to those of RING domains of other E3 ubiquitinases. The MUL1-RING domain adopts a ???? fold with three anti-parallel ?-strands and one ?-helix, containing a canonical cross-brace motif for the ligation of two zinc ions. Through NMR chemical shift perturbation experiments, we determined the p53-TAD-binding site in the MUL1-RING domain and showed that the MUL1-RING domain interacts mainly with the p53-TAD2 subdomain composed of residues 39-57. Taken together, our results provide a molecular basis for the novel recognition mechanism of the p53-TAD substrate by the MUL1-RING domain.
Mesh Terms:
Amino Acid Sequence, Humans, Magnetic Resonance Spectroscopy, Protein Binding, RING Finger Domains, Substrate Specificity, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination
Amino Acid Sequence, Humans, Magnetic Resonance Spectroscopy, Protein Binding, RING Finger Domains, Substrate Specificity, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination
Biochem. Biophys. Res. Commun.
Date: Dec. 20, 2018
PubMed ID: 31235254
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