Structure-activity relationships of calcicludine and dendrotoxin-I, homologous peptides acting on different targets, calcium and potassium channels.
Calcicludine (CaC) and dendrotoxin-I (DTX-I) possess high homology of their primary structures despite their different biological activities acting on calcium and potassium channels, respectively. In order to elucidate the channel specificity displayed by these toxins, their three-dimensional structures were compared by NMR. These analyses revealed that their overall conformations are similar except for the structure at the N-terminus. To demonstrate the significance of this N-terminal, chimeric peptides, CaC(1-30)/DTX-I(31-60) and DTX-I(1-30)/CaC(31-60), were synthesized. The CD spectra and receptor-binding measurements of chimeric peptides indicated that the contribution to the overall conformation and to the affinity of the N-terminal part of molecule seem to be more important than that of the C-terminal one. These results suggest that the N-terminal part may participate in distinguishing between calcium and potassium channels.
Nishio
H
H
Protein Research Foundation, Peptide Institute Inc., Osaka, Minoh-shi, 562-8686, Japan.
Katoh
E
E
Yamazaki
T
T
Inui
T
T
Nishiuchi
Y
Y
Kimura
T
T
D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000187:drug effects*; D002942:Circular Dichroism; D004220:Disulfides; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology*
D015220:Calcium Channels; D004220:Disulfides; D004546:Elapid Venoms; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D014118:Toxins, Biological; C085673:calcicludin; C108582:dendrotoxin I; C042467:dendrotoxin receptor