Structural Basis of Protein Kinase C alpha Regulation by the C-Terminal Tail | Academic Article individual record

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 PKCα 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.

author list (cited authors)
Yang, Y., Shu, C., Li, P., & Igumenova, T. I.
publication date
Elsevier bv Publisher
published in
Biophys J Journal
  • Static Electricity
  • Amino Acid Sequence
  • Protein Kinase C-alpha
  • Animals
  • Protein Domains
  • Calcium
  • Rats
  • Amino Acid Motifs
  • Hydrophobic And Hydrophilic Interactions
  • Mutation
citation count