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Molecular mechanism of K65 acetylation-induced attenuation of Ubc9 and the NDSM interaction
- Molecular mechanism of K65 acetylation-induced attenuation of Ubc9 and the NDSM interaction
- Naik, Mandar T; Kang, Moo Seok; Ho, ChunChen; Liao, Pei Hsin; Hsieh, Yung-Lin; Naik, Nandita M; Wang, Szu Huan; Chang, Ik Soo; Shih, Hsiu Ming; Huang, Tai Huang
- DGIST Authors
- Chang, Ik Soo
- Issue Date
- Scientific Reports, 7(1)
- Article Type
- UBIQUITIN-CONJUGATING ENZYME; PROTEIN-PROTEIN DOCKING; SUMO CONJUGATION; E3 LIGASE; SITE; SPECIFICITY; COMPLEX; BINDING; E2; PHOSPHORYLATION
- The negatively charged amino acid-dependent sumoylation motif (NDSM) carries an additional stretch of acidic residues downstream of the consensus Ψ-K-x-E/D sumoylation motif. We have previously shown that acetylation of the SUMO E2 conjugase enzyme, Ubc9, at K65 downregulates its binding to the NDSM and renders a selective decrease in sumoylation of substrates with the NDSM motif. Here, we provide detailed structural, thermodynamic, and kinetics results of the interactions between Ubc9 and its K65 acetylated variant (Ac-Ubc9K65) with three NDSMs derived from Elk1, CBP, and Calpain2 to rationalize the mechanism beneath this reduced binding. Our nuclear magnetic resonance (NMR) data rule out a direct interaction between the NDSM and the K65 residue of Ubc9. Similarly, we found that NDSM binding was entropy-driven and unlikely to be affected by the negative charge by K65 acetylation. Moreover our NMR, mutagenesis and molecular dynamics simulation studies defined the sequence of the NDSM as Ψ-K-x-E/D-x1-x2-(x3/E/D)-(x4/E/D)-xn and determined that K74 and K76 were critical Ubc9 residues interacting with the negatively charged residues of the NDSM. © 2017 The Author(s).
- NATURE PUBLISHING GROUP
- Related Researcher
Theoretical and Computational Biophysics Laboratory
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- Department of Brain and Cognitive SciencesTheoretical and Computational Biophysics Laboratory1. Journal Articles
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