| Summary: | Snakes contain three types of phospholipase A<sub>2</sub> (PLA<sub>2</sub>)-inhibitory proteins in their blood, PLIα, β, and γ, which protect them from their own venom, PLA<sub>2</sub>. PLIβ is the snake ortholog of leucine-rich α<sub>2</sub> glycoprotein (LRG). Since autologous cytochrome <i>c</i> (Cyt <i>c</i>) serves as an endogenous ligand for LRG, in this study, we purified snake LRGs from various snake serum samples using Cyt <i>c</i> affinity chromatography. All purified snake LRGs were found to be dimers linked by disulfide bonds. <i>Laticauda semifasciata</i> and <i>Naja kaouthia</i> LRGs showed no inhibitory activity against <i>L. semifasciata</i> PLA<sub>2</sub> and weak inhibitory activity against <i>Gloydius brevicauda</i> basic PLA<sub>2</sub>. <i>Elaphe climacophora</i> PLIβ had weaker inhibitory activity against <i>G. brevicauda</i> basic PLA<sub>2</sub> than <i>G. brevicauda</i> and <i>Elaphe quadrivirgata</i> PLIs, which are abundant in blood and known to neutralize <i>G. brevicauda</i> basic PLA<sub>2</sub>. <i>Protobothrops flavoviridis</i> LRG showed no inhibitory activity against basic venom PLA<sub>2</sub>, PL-X, or <i>G. brevicauda</i> basic PLA<sub>2</sub>. Binding analysis of <i>P. flavoviridis</i> LRG using surface plasmon resonance showed very strong binding to snake Cyt <i>c</i>, followed by that to horse Cyt <i>c</i>, weak binding to yeast Cyt <i>c</i>, and no binding to <i>P. flavoviridis</i> PL-X or BPI/II. We also deduced the amino acid sequences of <i>L. semifasciata</i> and <i>P. flavoviridis</i> LRG by means of cDNA sequencing and compared them with those of other known sequences of PLIs and LRGs. This study concluded that snake LRG can potentially inhibit basic PLA<sub>2</sub>, but, whether it actually functions as a PLA<sub>2</sub>-inhibitory protein, PLIβ, depends on the snake.
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