A novel alpha conotoxin (alpha-PIB) isolated from C. purpurascens is selective for skeletal muscle nicotinic acetylcholine receptors.
The alpha-conotoxin family is comprised of peptides that share the following arrangement of cysteine residues in the primary amino acid sequence: -CC-C-C-, where each dash represents a variable number of amino acids. The number of amino acids between cysteine residues has been used to group the alpha-conotoxins into distinct subfamilies. These subfamilies include the alpha 4/7-, alpha 4/3- and alpha 3/5-conotoxins, so named for the number of amino acids between 2nd/3rd and 3rd/4th cysteine residues, respectively. The alpha 3/5-conotoxins antagonize vertebrate-muscle nicotinic acetylcholine receptors (nAChRs), while the alpha 4/7- and alpha 4/3-conotoxins primarily inhibit vertebrate neuronal nAChRs. To date, these three subfamilies are the most extensively characterized of the alpha-conotoxin family. Here we report the purification and characterization of an unusual alpha 4/4-conotoxin, alpha-conotoxin PIB (alpha-PIB), from the venom of Conus purpurascens, with the following amino-acid sequence: ZSOGCCWNPACVKNRC (Z=pyroglutamate, O=hydroxyproline). This peptide demonstrates high affinity inhibition of vertebrate-muscle nAChRs, and paralytic effects when injected in vivo. Testing of alpha-PIB against other receptors indicated that the inhibitory effect is specific for skeletal muscle nAChRs. alpha-PIB shares the key biochemical and pharmacological characteristics of the alpha-conotoxin family.
López-Vera
Estuardo
E
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
Jacobsen
Richard B
RB
Ellison
Michael
M
Olivera
Baldomero M
BM
Teichert
Russell W
RW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D020916:Conotoxins / Q000235:genetics* / Q000633:toxicity*; D052078:Conus Snail / Q000737:chemistry*; D004594:Electrophysiology; D006054:Goldfish; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D020916:Conotoxins; D018733:Nicotinic Antagonists