Molecular Structure of Canine Cardiac Phospholamban, the Regulatory Protein of Ca Pump ATPase of Sarcoplasmic Reticulum
The excitation-contraction coupling of the myocardium represents a three-part process, involving three kinds of subcellular systems. These are sarcolemma, sarcoplasmic reticulum (SR), and myofibrillar proteins. Information transfer among these systems is exclusively carried out by Ca ions (Tadaet al., 1978), in that both membranes of sarcolemma and SR exhibit bidirectional Ca fluxes and the myofibrillar system contains the Ca receptor protein troponin. It is important to note that all of these three subcellular systems provide phosphorylation sites for protein kinases and, in addition, such phosphorylation reactions are thought to accompany profound alterations in Ca-related events in these systems. Among these, phosphorylation of phospholamban and its functional consequences are extensively defined (Tada and Katz, 1982; Tadaet al., 1982) in that phospholamban presumably serves to modulate the Ca pump ATPase of SR by augmenting the key elementary steps of ATPase (Tadaet al., 1979, 1980). Based on steady-state and presteady-state kinetic analysis of the Ca pump ATPase, phospholamban was proposed to function as a regulatory cofactor of the Ca pump ATPase type I, found in SR of cardiac and slow-contracting skeletal muscles (Kirchberger and Tada, 1976; Jorgensen and Jones, 1986). This is in contrast to the finding that SR of fast-contracting skeletal muscle, having type II Ca pump ATPase, is devoid of phospholamban. Phospholamban of cardiac SR was purified to near homogeneity and was sequenced by amino acid sequencing and by cDNA sequencing, demonstrating unique mo lecular properties. This paper defines the structural characteristics of phospholamban in its purified form and attempts to propose a molecular model for the functioning unit of phospholamban to understand, at least partly, the molecular mechanism by which the Ca pump ATPase is controlled by the phosphorylation of phospholamban.
KeywordsSarcoplasmic Reticulum High Pressure Liquid Chromatography Partial Amino Acid Sequence Cardiac Sarcoplasmic Reticulum Sarcoplasmic Reticulum Protein
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