Key result
Site-directed mutagenesis identified six residues of SERCA2 (Lys-Asp-Asp-Lys-Pro-Val402) and the cytoplasmic region of PLN as essential for their interaction.
Identifies the specific molecular interaction sites between phospholamban and SERCA2, as well as the transcriptional elements regulating phospholamban expression in cardiac cells.
These residues enable targeted modulation studies; leaves open effects on cardiac calcium handling or failure therapies.
Ca-ATPase regulates intracellular Ca levels by pumping Ca into sarcoplasmic reticulum. Phospholamban (PLN) functions as an inhibitory cofactor for cardiac Ca-ATPase (SERCA2). To define the molecular mode of interaction between two proteins, interaction sites have been identified. Studies using photoactivated cross-linker and chimeric Ca-ATPase between SERCA2 and nonmuscle Ca-ATPase (SERCA3) indicated that potential binding residues are located just downstream of the active ATPase site (Asp351) of SERCA2. Site-directed mutagenesis study of this region showed that six residues, Lys-Asp-Asp-Lys-Pro-Val402, of SERCA2 are functionally important for the interaction. Further, mutagenesis study of PLN showed that the cytoplasmic region of PLN contains a potential binding site with SERCA2. The unique expression of PLN in cardiac cells has been analyzed by the transcriptional level of its gene using luciferase activity and Gel shift assays. CCAAT-box in the 5'-upstream region was found to be essential for its expression by associating with Y-box binding transcriptional factors.
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Tada et al. (1998) studied Cardiac Ca-ATPase regulation. Site-directed mutagenesis was evaluated on Molecular interaction between PLN and SERCA2. Site-directed mutagenesis identified six residues of SERCA2 (Lys-Asp-Asp-Lys-Pro-Val402) and the cytoplasmic region of PLN as essential for their interaction.
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