Structural Basis of Protein Kinase Cα Regulation by the C-Terminal Tail.
Biophys J
; 114(7): 1590-1603, 2018 04 10.
Article
in En
| MEDLINE
| ID: mdl-29642029
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 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C-alpha
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biophys J
Year:
2018
Type:
Article