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 pancreatic and inflammatory-type mammalian sPL(2)s, which might be the natural endogenous ligands of PLA(2) receptors. Primary structures of OS1, 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 addition, the binding properties of pancreatic sPLA(2) mutants to the M-type receptor have been analyzed. Residues within or close to the Ca2+-binding loop of pancreatic sPLA(2) are crucially involved in the binding step, although the presence of Ca2+ that is essential for the enzymatic activity is not required for binding to the receptor. These residues 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 receptor. 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 phospholipase is essential for the acquisition of binding properties to the M-type receptor.