An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity

Troy C. Krzysiak, Laurel Thomas, You Jin Choi, Sylvain Auclair, Yiqi Qian, Shan Luan, Stephanie M. Krasnow, Laura L. Thomas, Leonardus M.I. Koharudin, Panayiotis V. Benos, Daniel L. Marks, Angela M. Gronenborn, Gary Thomas

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The disordered SIRT1 N-terminal region contains an insulin-responsive sensor (IRS), comprising an acidic cluster (AC) and a 3-helix bundle (3HB), controlling enzyme activity. Insulin triggers DBC1 and PACS-2 binding to the IRS. DBC1 removes the protective shield that hides the IRS, enabling PACS-2 to bind the acidic cluster and the 3-helix bundle, inhibiting SIRT1.

Original languageEnglish (US)
Pages (from-to)985-998.e7
JournalMolecular Cell
Volume72
Issue number6
DOIs
StatePublished - Dec 20 2018

    Fingerprint

Keywords

  • 3-helix bundle
  • AKT
  • FGF21
  • NMR spectroscopy
  • PACS2
  • PGC-1alpha
  • PPARalpha
  • STACs
  • diet-induced obesity
  • liver
  • nuclear magnetic resonance spectroscopy
  • small molecule sirtuin-activating compounds

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Krzysiak, T. C., Thomas, L., Choi, Y. J., Auclair, S., Qian, Y., Luan, S., Krasnow, S. M., Thomas, L. L., Koharudin, L. M. I., Benos, P. V., Marks, D. L., Gronenborn, A. M., & Thomas, G. (2018). An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity. Molecular Cell, 72(6), 985-998.e7. https://doi.org/10.1016/j.molcel.2018.10.007