title: Rattlesnake presynaptic neurotoxins: primary structure and evolutionary origin of the acidic subunit.
abstract: Crotoxin and homologous crotalid presynaptic neurotoxins consist of a toxic, basic subunit and a slightly smaller, nontoxic, acidic subunit. The latter, in turn, consists of three chains, interconnected by disulfide bonds. The complete sequences of two of the three acidic subunit chains of crotoxin, from the venom of the South American rattlesnake Crotalus durissus terrificus, have been determined. In addition, all but the ten amino-terminal residues of the third chain have been sequenced. Sequence comparison data suggest that the acidic subunit has been derived from a nontoxic, homodimeric, crotalid phospholipase A2. When compared with sequences of phospholipases A2, the acidic subunit lacks a 22-residue amino-terminal segment and two additional segments that are implicated in phospholipid substrate binding. However, it apparently retains an intact active site, the calcium binding loop, and segments involved in subunit binding in homodimeric phospholipases A2. The C chain of the acidic subunit shows strong homology with mammalian neurophysins, lending possible support to the hypothesis that the acidic subunit functions as a chaperone to prevent nonspecific binding of the toxic basic subunit. Crystals suitable for X-ray diffraction studies have recently been produced [Achari, A., Radvanyi, F. R., Scott, D., Bon, C., & Sigler, P. B. (1985) J. Biol. Chem. 260, 9385-9387]; thus with these data it should now be possible to determine the three-dimensional structure of the intact neurotoxin and dissociated subunits.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D003435:Crotalid Venoms / Q000235:genetics*; D003439:Crotoxin / Q000235:genetics*; D046911:Macromolecular Substances; D009498:Neurotoxins; D013045:Species Specificity
chemical_list: D003435:Crotalid Venoms; D046911:Macromolecular Substances; D009498:Neurotoxins; D003439:Crotoxin