Key result
Crystallography and mutagenesis identify a K+-binding site in the SERCA P-domain crucial for dephosphorylation.
Identifies the K+ binding site in SERCA, providing structural insights into its role in the dephosphorylation process.
May guide SERCA modulator design in HF; extends structural insights but leaves clinical translation open.
K+ plays an important role for the function of the sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA), but its binding site within the molecule has remained unidentified. We have located the binding site for a K+ ion in the P-domain by means of x-ray crystallography using crystals prepared in the presence of the K+ congener Rb+. Backbone carbonyls from the loop containing residues 711-715 together with the side chain of Glu732 define the K+/Rb+ site in the Ca2+ -ATPase conformation with bound Ca2+, ADP, and AlF4-. Functional analysis of Ca2+ -ATPase mutants with alterations to Glu732 shows that this site is indeed important for the stimulatory effect of K+ on the dephosphorylation rate. Comparison with the Ca2+ -ATPase in a dephosphorylated E2 conformation suggests that the K+ site is involved in the correct movement and positioning of the A-domain during translocation and dephosphorylation.
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Sørensen et al. (2004) studied this question. Ca2+-ATPase mutants with alterations to Glu732 was evaluated on Dephosphorylation rate. X-ray crystallography and mutagenesis of Glu732 identified a K+-binding site in the P-domain of the sarco(endo)plasmic reticulum Ca2+-ATPase that is important for its dephosphorylation rate.
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