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Snake alpha-neutotoxins of Elapidae venoms are grouped into two structural classes, short-chain and long-chain alpha-neutotoxins. While these two classes share many chemical and biological characteristics, there are also distinct dissimilarities between them, including their binding site on the nicotinic acetylcholine receptor (nAChR), specificity among species of Chordata, and the associated pharmacological effects. In the present study we test the hypothesis that structural motifs that evolved to confer natural resistance against conspecific long-chain alpha-neurotoxins in Elapidae snakes also interfere with the biological action of short-chain alpha-neurotoxins. We expressed functional nAChRs that contains segments or single residues of the Elapidae nAChR ligand binding domain and tested the effect of short-chain alpha-neurotoxin erabutoxin-a (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine-induced currents as measured by two-microelectrode voltage clamp. Our results show that the Elapidae nAChR alpha subunit segment T(154)-L(208) ligand binding domain has an inhibitory effect on the pharmacological action of ETX-a. This effect is primarily attributed to the presence of glycosylation at position N(189). If the glycosylation is removed from the T(154)-L(208) segment, the nAChR will be inhibited, however, to a lesser extent than seen in the mouse. This effect correlates with the variations in alpha-neurotoxin sensitivity of different species and, importantly, reflects the evolutionary conservation of the binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of alpha-neurotoxin resistance suggests that alpha-neurotoxin-resistant nAChR evolved first, which permitted the evolution of snake venom alpha-neurotoxins. A model describing alpha-neurotoxin resistance in Elapidae snakes is presented.
Ackermann,
Identification of pairwise interactions in the alpha-neurotoxin-nicotinic acetylcholine receptor complex through double mutant cycles.
1998, Pubmed
Ackermann,
Identification of pairwise interactions in the alpha-neurotoxin-nicotinic acetylcholine receptor complex through double mutant cycles.
1998,
Pubmed
Ackermann,
Nonidentity of the alpha-neurotoxin binding sites on the nicotinic acetylcholine receptor revealed by modification in alpha-neurotoxin and receptor structures.
1997,
Pubmed
Barchan,
The binding site of the nicotinic acetylcholine receptor in animal species resistant to alpha-bungarotoxin.
1995,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Burden,
Acetylcholine receptors at neuromuscular synapses: phylogenetic differences detected by snake alpha-neurotoxins.
1975,
Pubmed
Charpentier,
Recognition of the acetylcholine receptor binding site of a long-chain neurotoxin by toxin-specific monoclonal antibodies.
1990,
Pubmed
Chaturvedi,
Substitution of Torpedo acetylcholine receptor alpha 1-subunit residues with snake alpha 1- and rat nerve alpha 3-subunit residues in recombinant fusion proteins: effect on alpha-bungarotoxin binding.
1992,
Pubmed
Chaturvedi,
Effects of mutations of Torpedo acetylcholine receptor alpha 1 subunit residues 184-200 on alpha-bungarotoxin binding in a recombinant fusion protein.
1993,
Pubmed
Chicheportiche,
Structure-function relationship in the binding of snake neurotoxins to the torpedo membrane receptor.
1975,
Pubmed
Daly,
Levels of batrachotoxin and lack of sensitivity to its action in poison-dart frogs (Phyllobates).
1980,
Pubmed
Forstner,
Support for the hypothesis of anguimorph ancestry for the suborder Serpentes from phylogenetic analysis of mitochondrial DNA sequences.
1995,
Pubmed
Fry,
Molecular evolution and phylogeny of elapid snake venom three-finger toxins.
2003,
Pubmed
Fuchs,
Molecular evolution of the binding site of the acetylcholine receptor.
1993,
Pubmed
Fulachier,
Interaction of protein ligands with receptor fragments. On the residues of curaremimetic toxins that recognize fragments 128-142 and 185-199 of the alpha-subunit of the nicotinic acetylcholine receptor.
1994,
Pubmed
Ishikawa,
Acetylcholine receptors of human skeletal muscle: a species difference detected by snake neurotoxins.
1985,
Pubmed
Kachalsky,
Two subsites in the binding domain of the acetylcholine receptor: an aromatic subsite and a proline subsite.
1995,
Pubmed
Kaneko,
TTX resistivity of Na+ channel in newt retinal neuron.
1997,
Pubmed
Karlin,
Emerging structure of the nicotinic acetylcholine receptors.
2002,
Pubmed
Keller,
Molecular determinants conferring alpha-toxin resistance in recombinant DNA-derived acetylcholine receptors.
1995,
Pubmed
Keogh,
Phylogenetic relationships of terrestrial Australo-Papuan elapid snakes (subfamily Hydrophiinae) based on cytochrome b and 16S rRNA sequences.
1998,
Pubmed
Kornfeld,
Comparative aspects of glycoprotein structure.
1976,
Pubmed
Kreienkamp,
Glycosylation sites selectively interfere with alpha-toxin binding to the nicotinic acetylcholine receptor.
1994,
Pubmed
Lee,
Modes of actions of purified toxins from elapid venoms on neuromuscular transmission.
1966,
Pubmed
Legros,
The myth of scorpion suicide: are scorpions insensitive to their own venom?
1998,
Pubmed
Liu,
Lack of the blocking effect of cobrotoxin from Naja naja atra venom on neuromuscular transmission in isolated nerve muscle preparations from poisonous and non-poisonous snakes.
1990,
Pubmed
Love,
The crystal structure of alpha-bungarotoxin at 2.5 A resolution: relation to solution structure and binding to acetylcholine receptor.
1986,
Pubmed
Low,
X-ray crystallographic study of the erabutoxins and of a diiodo derivative.
1971,
Pubmed
Low,
Three dimensional structure of erabutoxin b neurotoxic protein: inhibitor of acetylcholine receptor.
1976,
Pubmed
Malany,
Orientation of alpha-neurotoxin at the subunit interfaces of the nicotinic acetylcholine receptor.
2000,
Pubmed
McLane,
Structural determinants of alpha-bungarotoxin binding to the sequence segment 181-200 of the muscle nicotinic acetylcholine receptor alpha subunit: effects of cysteine/cystine modification and species-specific amino acid substitutions.
1991,
Pubmed
Mebs,
Purification, properties and amino acid sequence of -bungarotoxin from the venom of Bungarus multicinctus.
1972,
Pubmed
Neumann,
Snake acetylcholine receptor: cloning of the domain containing the four extracellular cysteines of the alpha subunit.
1989,
Pubmed
Neumann,
Analysis of ligand binding to the synthetic dodecapeptide 185-196 of the acetylcholine receptor alpha subunit.
1986,
Pubmed
Négrerie,
Interaction of modified neurotoxins from Naja nigricollis with the nicotinic acetylcholine receptor from Torpedo marmorata. A Raman spectroscopy study.
1991,
Pubmed
Ohana,
Molecular dissection of cholinergic binding sites: how do snakes escape the effect of their own toxins?
1991,
Pubmed
Ovadia,
Neutralization of Viperidae and Elapidae snake venoms by sera of different animals.
1977,
Pubmed
Ruan,
The short-neurotoxin-binding regions on the alpha-chain of human and Torpedo californica acetylcholine receptors.
1991,
Pubmed
Sato,
The amino acid sequences of erabutoxins, neurotoxic proteins of sea-snake (Laticauda semifasciata) venom.
1971,
Pubmed
Sine,
The nicotinic receptor ligand binding domain.
2002,
Pubmed
Slowinski,
Phylogenetic relationships of elapid snakes based on cytochrome b mtDNA sequences.
2000,
Pubmed
Spura,
Biotinylation of substituted cysteines in the nicotinic acetylcholine receptor reveals distinct binding modes for alpha-bungarotoxin and erabutoxin a.
2000,
Pubmed
Stiles,
Acetylcholine receptor binding characteristics of snake and cone snail venom postsynaptic neurotoxins: further studies with a non-radioactive assay.
1993,
Pubmed
Stiles,
Characterization of monoclonal antibodies against Naja naja oxiana neurotoxin I.
1994,
Pubmed
Straight,
Antivenom activity of rattlesnake blood plasma.
1976,
Pubmed
Takacs,
Snake alpha-neurotoxin binding site on the Egyptian cobra (Naja haje) nicotinic acetylcholine receptor Is conserved.
2001,
Pubmed
,
Xenbase
Tamiya,
The isolation, properties and amino acid sequence of erabutoxin c, a minor neurotoxic component of the venom of a sea snake Katicauda semifasciata.
1972,
Pubmed
Teixeira-Clerc,
How do short neurotoxins bind to a muscular-type nicotinic acetylcholine receptor?
2002,
Pubmed
Tsernoglou,
The crystal structure of a post-synaptic neurotoxin from sea snake at A resolution.
1976,
Pubmed
Vincent,
Alpha-Bungarotoxin binding to human muscle acetylcholine receptor: measurement of affinity, delineation of AChR subunit residues crucial to binding, and protection of AChR function by synthetic peptides.
1998,
Pubmed
Wagh,
Sugar residues on proteins.
1981,
Pubmed
Weber,
Binding of Naja nigricollis (3H)alpha-toxin to membrane fragments from Electrophorus and Torpedo electric organs. I. Binding of the tritiated alpha-neurotoxin in the absence of effector.
1974,
Pubmed
Wilcox,
Phylogenetic relationships of the dwarf boas and a comparison of Bayesian and bootstrap measures of phylogenetic support.
2002,
Pubmed
Yoshida,
Tetrodotoxin-resistant sodium channels.
1994,
Pubmed