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+)-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.
Morrissette
J
J
Department of Physiology, University of Wisconsin School of Medicine, Madison 53706, USA.
Krätzschmar
J
J
Haendler
B
B
el-Hayek
R
R
Mochca-Morales
J
J
Martin
B M
BM
Patel
J R
JR
Moss
R L
RL
Schleuning
W D
WD
Coronado
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D008051:Lipid Bilayers; D008116:Lizards; D008564:Membrane Potentials / Q000187:drug effects; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015345:Oligonucleotide Probes; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018076:DNA, Complementary; D008051:Lipid Bilayers; D009124:Muscle Proteins; D015345:Oligonucleotide Probes; D010455:Peptides; D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014118:Toxins, Biological; C064223:helothermine; D012433:Ryanodine