title: The physical mechanism of calcium pump regulation in the heart.
abstract: The Ca-ATPase in the cardiac sarcoplasmic reticulum membrane is regulated by an amphipathic transmembrane protein, phospholamban. We have used time-resolved phosphorescence anisotropy to detect the microsecond rotational dynamics, and thereby the self-association, of the Ca-ATPase as a function of phospholamban phosphorylation and physiologically relevant calcium levels. The phosphorylation of phospholamban increases the rotational mobility of the Ca-ATPase in the sarcoplasmic reticulum bilayer, due to a decrease in large-scale protein association, with a [Ca2+] dependence parallel to that of enzyme activation. These results support a model in which phospholamban phosphorylation or calcium free the enzyme from a kinetically unfavorable associated state.
authors.affiliation: Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455.
authors.forename: J
authors.initials: J
authors.lastname: Voss
authors.forename: L R
authors.initials: LR
authors.lastname: Jones
authors.forename: D D
authors.initials: DD
authors.lastname: Thomas
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D004285:Dogs; D005454:Fluorescence Polarization; D006321:Heart / Q000502:physiology*; D007700:Kinetics; D049449:Luminescence; D008954:Models, Biological; D008961:Models, Structural; D010766:Phosphorylation; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D013997:Time Factors; D000099211:Phospholamban
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000099211:Phospholamban