Two novel toxins from the venom of the scorpion Pandinus imperator show that the N-terminal amino acid sequence is important for their affinities towards Shaker B K+ channels.
Two novel peptides were purified from the venom of the scorpion Pandinus imperator, and were named Pi2 and Pi3. Their complete primary structures were determined and their blocking effects on Shaker B K+ channels were studied. Both peptides contain 35 amino acids residues, compacted by three disulfide bridges, and reversibly block the Shaker B K+ channels. They have only one amino acid changed in their sequence, at position 7 (a proline for a glutamic acid). Whereas peptide Pi2, containing the Pro7, binds the Shaker B K+ channels with a Kd of 8.2 nm, peptide Pi3 containing the Glu7 residue has a much lower affinity of 140 nm. Both peptides are capable of displacing the binding of 125I-noxiustoxin to brain synaptosome membranes. Since these two novel peptides are about 50% identical to noxiustoxin, the present results support previous data published by our group showing that the amino-terminal region of noxiustoxin, and also the amino-terminal sequence of the newly purified homologues: Pi2, and Pi3, are important for the recognition of potassium channels.
Gómez-Lagunas
F
F
Department of Molecular Recognition, Universidad Nacional Autónoma de México, Cuernavaca 62271, Mexico.
Olamendi-Portugal
T
T
Zamudio
F Z
FZ
Possani
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D017924:Nucleopolyhedroviruses / Q000235:genetics; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D012605:Scorpions / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels; D018411:Spodoptera / Q000166:cytology; D013329:Structure-Activity Relationship
D018076:DNA, Complementary; C101360:Pi2 toxin; C101361:Pi3 toxin, scorpion; D015221:Potassium Channels; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels; C052567:noxiustoxin