Interhelical hydrogen bonds in transmembrane region are important for function and stability of Ca2+-transporting ATPase.

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Ca2+-transporting adenosine triphosphatase (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 Ca2+. The resulting calcium-free conformation (E2) is less stable than the E1 form. The changes in van der Waals interactions and interhelical hydrogen bonding in the E1 and E2 conformations were compared. Conformational changes in the transmembrane region concomitant with the release of Ca2+ mainly affect the number of interhelical hydrogen bonds, which is reduced to half of that in E1 form, whereas the number of interhelical atomic pairwise contacts reflecting van der Waals interactions experience little change. The interhelical hydrogen bonds in Ca2+-transporting ATPase can be divided into two groups according to their roles: those that play a structural stabilizing role and those that are important for the correct geometry of the Ca2+ binding site. Interhelical hydrogen bonds in the transmembrane 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.