title: Homologous kappa-neurotoxins exhibit residue-specific interactions with the alpha 3 subunit of the nicotinic acetylcholine receptor: a comparison of the structural requirements for kappa-bungarotoxin and kappa-flavitoxin binding.
abstract: kappa-Flavotoxin (kappa-FTX), a snake neurotoxin that is a selective antagonist of certain neuronal nicotinic acetylcholine receptors (AChRs), has recently been isolated and characterized [Grant, G. A., Frazier, M. W., & Chiappinelli, V. A. (1988) Biochemistry 27, 1532-1537]. Like the related snake toxin kappa-bungarotoxin (kappa-BTX), kappa-FTX binds with high affinity to alpha 3 subtypes of neuronal AChRs, even though there are distinct sequence differences between the two toxins. To further characterize the sequence regions of the neuronal AChR alpha 3 subunit involved in formation of the binding site for this family of kappa-neurotoxins, we investigated kappa-FTX binding to overlapping synthetic peptides screening the alpha 3 subunit sequence. A sequence region forming a "prototope" for kappa-FTX was identified within residues alpha 3 (51-70), confirming the suggestions of previous studies on the binding of kappa-BTX to the alpha 3 subunit [McLane, K. E., Tang, F., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 1537-1544] and alpha-bungarotoxin to the Torpedo AChR alpha subunit [Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230] that this sequence region is involved in formation of a cholinergic site. Single residue substituted analogues, where each residue of the sequence alpha 3 (51-70) was sequentially replaced by a glycine, were used to identify the amino acid side chains involved in the interaction of this prototope with kappa-FTX.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry, University of Minnesota, St. Paul 55108.
authors.forename: K E
authors.initials: KE
authors.lastname: McLane
authors.forename: W R
authors.initials: WR
authors.lastname: Weaver
authors.forename: S
authors.initials: S
authors.lastname: Lei
authors.forename: V A
authors.initials: VA
authors.lastname: Chiappinelli
authors.forename: B M
authors.initials: BM
authors.lastname: Conti-Tronconi
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology*; D004546:Elapid Venoms / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012911:Snakes; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D002038:Bungarotoxins; D004546:Elapid Venoms; D009498:Neurotoxins; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C052119:kappa-flavitoxin