Larsen, Erik2021-06-292021-06-292021-04https://hdl.handle.net/11299/220595University of Minnesota Ph.D. dissertation. 2021. Major: Chemistry. Advisor: Jiali Gao. 1 computer file (PDF); 244 pages.The Ca2+ transient of the cardiomyocyte is key to the contractility of the heart. Its dysregulation has been associated with heart disease, leading to investigation of the regulation of Ca2+ for potential drug targets. The Sarcoplasmic Endo-Reticulum Ca2+ ATP-ase (SERCA) pump and its main inhibitor in heart tissue, phospholamban (PLN), are two promising targets that are under β-adrenergic control via phosphorylation of PLN by Protein Kinase A (PKA). Phosphorylation of Ser16 on the cytoplasmic domain of PLN results in decreased inhibition of SERCA. Recently, an additional member of the SERCA interactome has been discovered called Hematopoietic lineage cell-specific protein 1 (HCLS1) Associated Protein X-1 (HAX-1). Contrasting PLN phosphorylation, the interaction of HAX-1 and PLN increases the inhibition of PLN for SERCA, adding another layer of complexity to SERCA regulation and a potential new drug target. This thesis aims to investigate the structure-function relationship of the ternary complex, SERCA/PLN/HAX-1 using NMR spectroscopy as the primary technique.enHAX-1Intrinsically Disordered ProteinsNuclear Magnetic ResonancePeripheral Membrane ProteinsPhospholambanSERCAThesis or Dissertation