Dynamic Response of the C2 Domain of Protein Kinase C to Ca2+ Binding. Academic Article uri icon


  • 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 C (C2) 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 C2. We propose that Ca2+ binding allosterically destabilizes the terminal regions of C2 and thereby facilitates the conformational rearrangement necessary for full membrane insertion and activation of protein kinase C.

published proceedings

  • Biophys J

altmetric score

  • 1

author list (cited authors)

  • Morales, K. A., Yang, Y., Cole, T. R., & Igumenova, T. I.

citation count

  • 10

complete list of authors

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

publication date

  • October 2016