Dynamic Response of the C2 Domain of Protein Kinase Cα to Ca2+ Binding.

Krystal A Morales, Yuan Yang, Taylor R Cole, Tatyana I Igumenova

Biophysical journal 2016 Oct 18

filter terms:

Ca2+-dependent conserved-region 2 (C2) domains target their host signaling proteins to anionic membranes. The Ca2+-binding event is a prerequisite for membrane association. Here, we investigate multiscale metal-ion-dependent dynamics of the C2 domain of protein kinase Cα (C2α) using NMR spectroscopy. Interactions with metal ions attenuate microsecond-timescale motions of the loop regions, indicating that preorganization of the metal-binding loops occurs before membrane insertion. Binding of a full complement of Ca2+ ions has a profound effect on the millisecond-timescale dynamics of the N- and C-terminal regions of C2α. We propose that Ca2+ binding allosterically destabilizes the terminal regions of C2α and thereby facilitates the conformational rearrangement necessary for full membrane insertion and activation of protein kinase Cα. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Citation

Krystal A Morales, Yuan Yang, Taylor R Cole, Tatyana I Igumenova. Dynamic Response of the C2 Domain of Protein Kinase Cα to Ca2+ Binding. Biophysical journal. 2016 Oct 18;111(8):1655-1667