Interhelical hydrogen bonds in transmembrane region are important for function and stability of Ca-transporting ATPase

Ca 2+-transporting ATPase of sarcoplasmic reticulum couples ATP hydrolysis with ion transport. Phosphorylation of the cytosolic region of the calcium-bound conformation (E1) of the protein leads to drastic conformational rearrangements of the transmembrane helices and the release of Ca 2+. The resulting calcium-free conformation (E2) is less stable than the E1 form. We compare the changes in van der Waals interactions and interhelical hydrogen bonding in the E1 and E2 conformations. We find that conformational changes in the transmembrane region concomitant with the release of Ca 2+ mainly affect the number of interhelical hydrogen bonds, which is reduced to half of that in E1 form, while the number of interhelical atomic pairwise contacts reflecting van der Waals interactions experience little change. The interhelical hydrogen bonds in Ca 2+-transporting ATPase can be divided into two groups according to their roles: those that play structural stabilizing role and those that are important for the correct geometry of the Ca 2+ binding site. We suggest that interhelical hydrogen bonds in the TM regions play important roles for the stability and specificity of helix-helix interactions in proteins where change of conformation is required for transport of ions or small molecules.