STRUCTURAL ELEMENTS OF SECRETORY PHOSPHOLIPASES A(2) INVOLVED IN THE BINDING TO M-TYPE RECEPTORS

Specific membrane receptors for secretory phospholipases A(2) (sPL(2)s ) have been initially identified with novel snake venom sPL(2)s called OS1 and OS2. One of these sPLA(2) receptors (muscle (M) type, 180 kDa ) has a very high affinity for OS1 and OS2 and a high affinity for pan creatic and inflammatory-type mammalian sPL(2)s, which might be the na tural endogenous ligands of PLA(2) receptors. Primary structures of OS 1, and OS2 were determined and compared with sequences of other sPL(2) s that bind less tightly or do not bind to the M-type receptor. In add ition, the binding properties of pancreatic sPLA(2) mutants to the M-t ype receptor have been analyzed. Residues within or close to the Ca2+- binding loop of pancreatic sPLA(2) are crucially involved in the bindi ng step, although the presence of Ca2+ that is essential for the enzym atic activity is not required for binding to the receptor. These resid ues include Gly-30 and Asp-49, which are conserved in all sPL(2)s. Leu -31 is also essential for binding of pancreatic sPLA(2) to its recepto r. Many other mutations have been considered. Those occurring in the N -terminal alpha helices and the pancreatic loop do not change binding to the M-type receptor. Conversion of pancreatic prophospholipase to p hospholipase is essential for the acquisition of binding properties to the M-type receptor.