PRIMARY STRUCTURE AND SYNTHESIS OF IMPERATOXIN-A (IPTX(A)), A PEPTIDEACTIVATOR OF CA2+ RELEASE CHANNELS RYANODINE RECEPTORS

We present the complete amino acid sequence of Imperatoxin A (IpTx(a)) , a 33-amino-acid peptide from the venom of the scorpion P. imperator which activates Ca2+ release channels/ryanodine receptors (RyR) of sar coplasmic reticulum (SR). The amino acid sequence of IpTx(a) shows no homology to any scorpion toxin so far described, but shares some homol ogy to the amino acid sequence of Tx2-9 and agelenin, two spider toxin s that target neuronal P-type Ca2+ channels. We also describe the tota l synthesis of IpTx(a) and demonstrate that it efficiently activates R yRs with potency and affinity identical to those of native IpTx(a). Th e use of synthetic IpTx(a) should help in the identification of the st ructural motifs of RyR critical for channel gating. (C) 1997 Federatio n of European Biochemical Societies.