Structural basis for the E1/E1P-E2/E2P conformation changes in the sarcoplasmic reticulum Ca(2+)-ATPase studied by site-specific mutagenesis.

Site-specific mutagenesis and functional expression of cloned cDNA of the sarcoplasmic reticulum Ca(2+)-ATPase have been used to demonstrate that exchange of single amino acid residues in the Ca(2+)-ATPase can lead to forms with either "E1/E1P" or "E2/E2P" characteristics. The localization of the mutated residues identifies the M4S4 segment of the ATPase molecule as central to the energy-tranducing conformation change, and on the basis of this information a model for the pump mechanism is discussed.