A novel alpha conotoxin (α-PIB) isolated from C. purpurascens is selective for skeletal muscle nicotinic acetylcholine receptors

Abstract The α -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 α -conotoxins into distinct subfamilies. These subfamilies include the α 4/7-, α 4/3- and α 3/5-conotoxins, so named for the number of amino acids between 2nd/3rd and 3rd/4th cysteine residues, respectively. The α 3/5-conotoxins antagonize vertebrate-muscle nicotinic acetylcholine receptors (nAChRs), while the α 4/7- and α 4/3-conotoxins primarily inhibit vertebrate neuronal nAChRs. To date, these three subfamilies are the most extensively characterized of the α -conotoxin family. Here we report the purification and characterization of an unusual α 4/4-conotoxin, α -conotoxin PIB ( α -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 α -PIB against other receptors indicated that the inhibitory effect is specific for skeletal muscle nAChRs. α -PIB shares the key biochemical and pharmacological characteristics of the α -conotoxin family.