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Molecular mechanism of K65 acetylation-induced attenuation of Ubc9 and the NDSM interaction

Title
Molecular mechanism of K65 acetylation-induced attenuation of Ubc9 and the NDSM interaction
Authors
Naik, Mandar TKang, Moo SeokHo, ChunChenLiao, Pei HsinHsieh, Yung-LinNaik, Nandita MWang, Szu HuanChang, Ik SooShih, Hsiu MingHuang, Tai Huang
DGIST Authors
Chang, Ik Soo
Issue Date
2017-12
Citation
Scientific Reports, 7(1)
Type
Article
Article Type
Article
Keywords
UBIQUITIN-CONJUGATING ENZYMEPROTEIN-PROTEIN DOCKINGSUMO CONJUGATIONE3 LIGASESITESPECIFICITYCOMPLEXBINDINGE2PHOSPHORYLATION
ISSN
2045-2322
Abstract
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).
URI
http://hdl.handle.net/20.500.11750/5625
DOI
10.1038/s41598-017-17465-0
Publisher
NATURE PUBLISHING GROUP
Related Researcher
  • Author   Theoretical and Computational Biophysics Laboratory
  • Research Interests
Files:
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Collection:
Department of Brain and Cognitive SciencesTheoretical and Computational Biophysics Laboratory1. Journal Articles


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