Conditional Membrane Proteins: Solution NMR Studies of Structure, Dynamics, and Function

Yang, Yuan; Morales, Krystal; Stewart, Mark; Igumenova, Tatyana I.

doi:10.1002/9780470034590.emrstm1415

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2016

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“…1 C). The loops are involved in the interactions with the membrane headgroup region, as was demonstrated using electron paramagnetic resonance and NMR spectroscopy (5,6).…”

Section: Introductionmentioning

confidence: 95%

Dynamic Response of the C2 Domain of Protein Kinase C α to Ca 2+ Binding

Morales

Yang

Cole

et al. 2016

Biophysical Journal

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Ca-dependent conserved-region 2 (C2) domains target their host signaling proteins to anionic membranes. The Ca-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 Ca ions has a profound effect on the millisecond-timescale dynamics of the N- and C-terminal regions of C2α. We propose that Ca 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.

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“…1 C). The loops are involved in the interactions with the membrane headgroup region, as was demonstrated using electron paramagnetic resonance and NMR spectroscopy (5,6).…”

Section: Introductionmentioning

confidence: 95%