THE PRECURSOR REGION OF A PROTEIN ACTIVE IN SPERM-EGG FUSION CONTAINSA METALLOPROTEASE AND A DISINTEGRIN DOMAIN - STRUCTURAL, FUNCTIONAL, AND EVOLUTIONARY IMPLICATIONS

PH-30, a sperm surface protein involved in sperm-egg fusion, is compos ed of two subunits, alpha and beta, which are synthesized as precursor s and processed, during sperm development, to yield the mature forms. The mature PH-30 alpha/beta complex resembles certain viral fusion pro teins in membrane topology and predicted binding and fusion functions. Furthermore, the mature subunits are similar in sequence to each othe r and to a family of disintegrin domain-containing snake venom protein s. We report here the sequences of the PH-30 alpha and beta precursor regions. Their domain organizations are similar to each other and to p recursors of snake venom metalloproteases and disintegrins. The alpha precursor region contains, from amino to carboxyl terminus, pro, metal loprotease, and disintegrin domains. The beta precursor region contain s pro and metalloprotease domains. Residues diagnostic of a catalytica lly active metalloprotease are present in the alpha, but not the beta, precursor region. We propose that the active sites of the PH-30 alpha and snake venom metalloproteases are structurally similar to that of astacin. PH-30, acting through its metalloprotease and/or disintegrin domains, could be involved in sperm development as well as sperm-egg b inding and fusion. Phylogenetic analysis indicates that PH-30 stems fr om a multidomain ancestral protein.