How lipids interact with an intrinsic membrane protein: the case of the calcium pump

Abstract

Ca²⁺-ATPase can be purified from the skeletal muscle of sarcoplasmic reticulum and reconstituted into phospholipid bilayers of defined composition. This allows a detailed study of the interactions between phospholipid molecules and the ATPase, and of the effects of phospholipid structure on the activity of the ATPase. It has been shown that the thickness of the lipid bilayer, its physical phase and the lipid headgroup structure can all be important. The interaction between phospholipids and the ATPase is not structurally specific in that the strength of the phospholipid-ATPase interaction does not depend on headgroup structure or on fatty acyl chain length, but the strength of binding is different for liquid crystalline and gel phase lipid. There are also ‘specific’ sites for some lipids on the ATPase. There is no unique mechanism explaining the effects of phospholipid on the function of the ATPase; the changes observed with any particular phospholipid follow from a distinct set of changes in the conformational state of the ATPase. The changes in activity are likely to follow from tilting of trans-membrane α-helices in the ATPase. In simple model systems it has been shown that the extent to which lipids can distort to match the protein is limited.