STRUCTURAL-CHANGES IN A SECRETORY PHOSPHOLIPASE A(2) INDUCED BY MEMBRANE-BINDING - A CLUE TO INTERFACIAL ACTIVATION

Activation of phospholipase A(2) (PLA(2)) upon binding to phospholipid assemblies is poorly understood. X-ray crystallography revealed littl e structural change in the enzyme upon binding of monomeric substrate analogs, whereas small conformational changes in PLA(2) complexed with substrate micelles and an inhibitor were found by NMR. The structure of PLA(2) bound to phospholipid bilayers is not known. Here we uncover by FTIR spectroscopy a splitting in the alpha-helical region of the a mide I absorbance band of PLA(2) upon binding to lipid bilayers. We pr ovide evidence that a higher frequency component, which is only observ ed in the membrane-bound enzyme, is a property of more flexible helice s. Formation of flexible helices upon interaction with the membrane is likely to contribute to PLA(2) activation. (C) 1997 Academic Press Li mited.