Role of C-terminal tail of long neurotoxins from snake venoms in molecular conformation and acetylcholine receptor binding: proton nuclear magnetic resonance and competition binding studies.
The role of the "C-terminal tail" segment of long neurotoxins has been investigated. The C-terminal four to five residues of alpha-bungarotoxin and Laticauda colubrina b have been cleaved off by carboxypeptidase P. The effect of such deletion on the toxin conformation has been monitored in proton nuclear magnetic resonance spectra and circular dichroism spectra. The removal of the C-terminal residues primarily affects the chemical shifts of proton resonances of the residues close to the cleavage site and does not induce a major conformational change. Therefore, the C-terminal tail of long neurotoxins does not appear to be important in maintaining the specific polypeptide chain folding. On the other hand, competition binding with tritium-labeled toxin alpha to Narke japonica acetylcholine receptor has revealed that cleavage of the C-terminal residues reduces the binding activity of alpha-bungarotoxin or Laticauda colubrina b to acetylcholine receptor. Thus it is likely that (the basic amino acid residues in) the C-terminal tail is directly involved in the binding of long neurotoxins to electric organ (and muscle) acetylcholine receptor.
Endo
T
T
Department of Chemistry, College of Technology, Gunma University, Kiryu, Japan.
Oya
M
M
Tamiya
N
N
Hayashi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism* / Q000494:pharmacology; D002942:Circular Dichroism; D004555:Electric Fish; D004557:Electric Organ / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D011487:Protein Conformation; D011950:Receptors, Cholinergic / Q000378:metabolism*; D030162:Reptilian Proteins; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D002038:Bungarotoxins; D009498:Neurotoxins; D011950:Receptors, Cholinergic; D030162:Reptilian Proteins; C053782:laticauda colubrina b