Structural changes in a secretory phospholipase A2 induced by membrane binding: a clue to interfacial activation?

Activation of phospholipase A2 (PLA2) upon binding to phospholipid assemblies is poorly understood. X-ray crystallography revealed little structural change in the enzyme upon binding of monomeric substrate analogs, whereas small conformational changes in PLA2 complexed with substrate micelles and an inhibitor were found by NMR. The structure of PLA2 bound to phospholipid bilayers is not known. Here we uncover by FTIR spectroscopy a splitting in the alpha-helical region of the amide I absorbance band of PLA2 upon binding to lipid bilayers. We provide evidence that a higher frequency component, which is only observed in the membrane-bound enzyme, is a property of more flexible helices. Formation of flexible helices upon interaction with the membrane is likely to contribute to PLA2 activation.