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The Physical And Mechanistic Basis For Calcium-Atpase Regulation By Phospholamban., Jason Shawn Southall

Graduate Theses, Dissertations, and Problem Reports (ETD)

The Ca-ATPase of sarcoplasmic reticulum is a 110 kDa integral membrane protein responsible for calcium transport from the cytosol into the sarcoplasmic reticulum lumen to promote muscle relaxation. In the heart, the Ca-ATPase is regulated by phospholamban, a 52 residue integral membrane protein, which inhibits the Ca-ATPase by decreasing the apparent calcium affinity of the enzyme. Phospholamban phosphorylation relieves Ca-ATPase inhibition. At present, the physical mechanism by which phospholamban regulates the Ca-ATPase is not known. The purpose of this dissertation research was to test the hypothesis that phospholamban regulates the CaATPase by altering Ca-ATPase protein-protein interactions that are important for …