title: Dynamic Response of the C2 Domain of Protein Kinase Cα to Ca2+Binding.
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 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.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas.
authors.forename: Krystal A
authors.initials: KA
authors.lastname: Morales
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas.
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Cole
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas. Electronic address: tigumenova@tamu.edu.
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Igumenova
mesh_terms: D000494:Allosteric Regulation; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D000070538:C2 Domains; D002118:Calcium / Q000378:metabolism*; D006860:Hydrogen Bonding; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001051:Apoenzymes; D008670:Metals; D051571:Protein Kinase C-alpha; D002118:Calcium