The spasmodic peptide defines a new conotoxin superfamily

We purified and characterized a peptide from the venom of Conus textile tha t makes normal mice assume the phenotype of a well-known mutant, the spasmo dic mouse. This "spasmodic" peptide has 27 amino acids, including two gamma -carboxyglutamate (Gla) residues. A cDNA clone encoding the precursor for t he peptide was identified; a gamma-carboxylation recognition signal sequenc e (gamma-CRS) is present in the -1 -> -20 region of the peptide precursor. Both the gamma-CRS and the position of the Gla residues in the mature toxin are notably different from other Gla-containing conopeptides. The spasmodi c peptide has a novel disulfide framework and distinct signal sequence whic h together define a new P-superfamily of conopeptides. A cDNA encoding anot her member of the P-superfamily was identified from a different species, Co nus gloriamaris.