Calcium Regulation by Phospholamban and Sarcolipin

Calcium re-uptake to the sarcoplasmic reticulum (SR) for muscle relaxation is primarily mediated by the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). SERCA’s ability to transport Ca2+ is modulated by two transmembrane proteins, phospholamban (PLN) and sarcolipin (SLN) depending on the tissue type. By employing magic-angle-spinning (MAS) and oriented solid-state NMR methods we aim to understand the unique regulatory mechanisms of PLN and SLN, and how their regulation of SERCA is perturbed by post-translational modifications and pathogenic mutations.

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CaM/RyR Binding and Regulation

Arrhythmogenic mutations and oxidative modifications in CaM have been linked to dysregulation of calcium release through the ryanodine receptor for muscle contraction. By combining solution and solid-state NMR techniques we aim to identify the structural basis for this dysregulation and build a residue and domain specific model for CaM’s binding and regulation of the RyR.

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