Primary structure and properties of helothermine, a peptide toxin that blocks ryanodine receptors

Helothermine, a protein from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to inhibit [3H]ryanodine binding to cardiac and skeletal sarcoplasmic reticulum, to block cardiac and skeletal ryanodine receptor channels incorporated into planar bilayers, and to block Ca(2...

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Bibliographic Details
Published in:Biophysical journal 1995-06, Vol.68 (6), p.2280-2288
Main Authors: Morrissette, J., Krätzschmar, J., Haendler, B., el-Hayek, R., Mochca-Morales, J., Martin, B.M., Patel, J.R., Moss, R.L., Schleuning, W.D., Coronado, R.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Binding, Competitive
Calcium Channel Blockers - chemistry
Calcium Channel Blockers - pharmacology
Calcium Channels - drug effects
Calcium Channels - physiology
Cloning, Molecular
DNA, Complementary
Lipid Bilayers
Lizards
Membrane Potentials - drug effects
Microsomes - metabolism
Molecular Sequence Data
Muscle Proteins - drug effects
Muscle Proteins - physiology
Muscle, Skeletal - metabolism
Myocardium - metabolism
Oligonucleotide Probes
Peptide Biosynthesis
Peptides - chemistry
Peptides - pharmacology
Rabbits
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Recombinant Proteins - pharmacology
Ryanodine - metabolism
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum - metabolism
Sequence Homology, Amino Acid
Swine
Toxins, Biological - chemistry
Toxins, Biological - pharmacology
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Summary:Helothermine, a protein from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to inhibit [3H]ryanodine binding to cardiac and skeletal sarcoplasmic reticulum, to block cardiac and skeletal ryanodine receptor channels incorporated into planar bilayers, and to block Ca(2+)-induced Ca2+ release triggered by photolysis of nitr-5 in saponin-permeabilized trabeculae from rat ventricle. Cloning of the helothermine cDNA revealed that the protein is composed of 223 amino acids with a molecular mass of 25,376 daltons, and apparently is stabilized by eight disulfide bridges. The peptide sequence showed significant homology with a family of cysteine-rich secretory proteins found in the male genital tract and in salivary glands. The interaction of helothermine and ryanodine receptors should serve to define functional domains within the channel structure involved in the control of Ca2+ release from sarcoplasmic reticulum.
ISSN:0006-3495
1542-0086
DOI:10.1016/S0006-3495(95)80410-8