Structure-Function Relationship of Hydrophiidae Postsynaptic Neurotoxins
Abstract
Lapemis toxin, from a Hydrophiidae sea snake venom (Lapemis hardwickii), binds tightly and specifically to the nicotinic acetylcholine receptor (AChR) inhibiting neumuscular transmission and results in muscular paralysis. In order to study the structure-function relationship of Lapemis toxin structural loop domains were synthesized. The domain peptide were found to be non-toxic at 8 mg/kg dosage (i.v., mice) or 114 times the known LD50 of Lapemis toxin. Binding studies with Torpedo californica acetylcholine receptor and 125-I radiolabelled toxin and peptides indicated that Lapemis toxin and peptide Bl bound with equilibrium dissociation constants of 2 nM and 40 nM, respectively. The other peptides had no detectable binding. Chemical modification study of which of the three arginines, located in the central loop, are involved in the neurotoxin-AChR demonstrated that Arg-31 and Arg-34 residues are involved in toxin-AChR interaction. The central loop B with intact disulfide bond of the native lapemis toxin appears to play a dominate role in the toxin's binding ability to the receptor. Characterization of the 9 kD and the 13.5 kD proteins fractionated from Lapemis hardwickii venom have been identified from partial sequence data as parvalbumin and phospholipase A2, respectively.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 11, 1992
- Accession Number
- ADA248729
Entities
People
- Anthony T. Tu
Organizations
- Colorado State University