Structural Basis of Protein Kinase C Regulation by the C-Terminal Tail. uri icon

abstract

  • Protein kinase C (PKC) isoenzymes are multi-modular proteins activated at the membrane surface to regulate signal transduction processes. When activated by second messengers, PKC undergoes a drastic conformational and spatial transition from the inactive cytosolic state to the activated membrane-bound state. The complete structure of either state of PKC remains elusive. We demonstrate, using NMR spectroscopy, that the isolated Ca2+-sensing membrane-binding C2 domain of the conventional PKC interacts with a conserved hydrophobic motif of the kinase C-terminal region, and we report a structural model of the complex. Our data suggest that the C-terminal region plays a dual role in regulating the PKC activity: activating, through sensitization of PKC to intracellular Ca2+ oscillations; and auto-inhibitory, through its interaction with a conserved positively charged region of the C2 domain.

published proceedings

  • Biophys J

author list (cited authors)

  • Yang, Y., Shu, C., Li, P., & Igumenova, T. I.

citation count

  • 3

complete list of authors

  • Yang, Yuan||Shu, Chang||Li, Pingwei||Igumenova, Tatyana I

publication date

  • January 2018