Identification and characterization of a serum protein homologous to alpha-type phospholipase A2 inhibitor (PLIalpha) from a nonvenomous snake, Elaphe quadrivirgata.

From a liver cDNA library prepared from a nonvenomous striated snake, Elaphe quadrivirgata, we isolated a cDNA encoding a novel protein, PLIalpha-like protein (PLIalpha-LP), having approximately 70% sequence identities with the alpha-type phospholipase A2 (PLA2) inhibitors (PLIalpha(s)) previously purified from the venomous snakes Agkistrodon blomhoffii siniticus and Trimeresurus flavoviridis. Since the PLI-LP with a highly conserved C-type lectin-like domain (CTLD) would be predicted to function as a PLA2 inhibitor, we purified this protein from E. quadrivirgata serum by sequential chromatography on Hi-trap Blue, Mono Q, and Superdex 200 columns. The purified 51-kDa protein with PLIalpha-like immunoreactivity was found to be a trimer of 18-kDa PLIalpha-LP, which was comparable to the trimeric structure of PLIalpha. But, unexpectedly, this protein did not show any inhibitory activity against various snake venom PLA2s. Furthermore, it did not inhibit the endogenous PLA2 activities in various tissue homogenates prepared from this snake. Lack of the inhibitory activity in PLIalpha-LP may provide important information concerning the structure-function relationships of PLIalpha.