title: Primary structure and synthesis of Imperatoxin A (IpTx(a)), a peptide activator of Ca2+ release channels/ryanodine receptors.
abstract: 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 sarcoplasmic reticulum (SR). The amino acid sequence of IpTx(a) shows no homology to any scorpion toxin so far described, but shares some homology to the amino acid sequence of Tx2-9 and agelenin, two spider toxins that target neuronal P-type Ca2+ channels. We also describe the total synthesis of IpTx(a) and demonstrate that it efficiently activates RyRs with potency and affinity identical to those of native IpTx(a). The use of synthetic IpTx(a) should help in the identification of the structural motifs of RyR critical for channel gating.
authors.affiliation: Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Cuernavaca, Morelos.
authors.forename: F Z
authors.initials: FZ
authors.lastname: Zamudio
authors.forename: G B
authors.initials: GB
authors.lastname: Gurrola
authors.forename: C
authors.initials: C
authors.lastname: Arévalo
authors.forename: R
authors.initials: R
authors.lastname: Sreekumar
authors.forename: J W
authors.initials: JW
authors.lastname: Walker
authors.forename: H H
authors.initials: HH
authors.lastname: Valdivia
authors.forename: L D
authors.initials: LD
authors.lastname: Possani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology*; D011485:Protein Binding; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000187:drug effects; D012604:Scorpion Venoms / Q000138:chemical synthesis / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; C105361:imperatoxin A; D002118:Calcium