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

abstract

• 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.

authors

• Igumenova, Tatyana

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

publisher

• Elsevier  Publisher

published in

• Biophysical Journal  Journal

keywords

• Allosteric Regulation
• Apoenzymes
• C2 Domains
• Calcium
• Hydrogen Bonding
• Metals
• Models, Molecular
• Protein Binding
• Protein Kinase C-alpha

PubMed Central ID

• 27760353

Digital Object Identifier (DOI)

• 10.1016/j.bpj.2016.09.008

start page

• 1655

end page

• 1667

volume

• 111

issue

• 8

URL

• http%3A%2F%2Fdx.doi.org%2F10.1016%2Fj.bpj.2016.09.008