Scorpion toxin binding

Bean Is there any relation to the scorpion toxin binding sites ... 

Catterall No. In photoaffinity experiments we observed labelling of both a and /il subunits. We can understand this now, because it is probably a bystander effect for the pi subunit. The scorpion toxin receptor site is certainly not on the subunit, and Na+ channels that have only an a subunit are fully sensitive to scorpion toxin, /il must be near enough to the a scorpion toxin binding site to be photolabelled as a bystander. One point of interaction of pi is the last extracellular loop, just outside the IV S6 segment. This is the extracellular loop exactly adjacent to the one that a scorpion toxin binds to, which is the S3/S4 loop in domain IV. We think the toxin sits there, the pi subunit is nearby and sometimes the photoprobe reaches over and covalently labels it. 

Tamkun MM, Talvenheimo JA, Catterall WA. The sodium channel from rat brain reconstitution of neurotoxin-activated ion flux and scorpion toxin binding from purified components. J Biol Chem 1984 259 1676-1688. 

Gasparini, S Gilquin, B and M ez, A. (2004) Comparison of sea anemone and scorpion toxins binding to Kvl channels an example of convergent evolution. Toxicon, 43,901-908. 

Arseniev, A.S. and Grishin, E.V. (2002) New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1. The... 

The scorpion a-toxins have been shown to bind to site 3 on the voltage-gated sodium channel [24,27,42]. These polypeptides contain up to 70 residues crosslinked by four disulfide bonds, but show no sequence similarity to the anemone polypeptides. Possible structural similarities have been discussed [24], and in a theoretical model of the anemone toxin Bg II, some of the cationic residues were in similar locations to those in the crystal structure of the scorpion toxin Aah II [26]. 

Ion channels have been purified from several types of excitable cells. The proteins that make up the voltage-gated Na+ channels of brain neurons were first identified by labeling them with reactive derivatives of neurotoxins obtained from scorpions. Intact channels were purified from both brain and muscle after solubilization with detergents. When the purified proteins were incorporated into phospholipid vesicles or planar bilayer membranes, they were found to conduct Na+ across the membrane. The ion specificity of the reconstituted channels and the alterations of the conductance in response to changes in Aift or to various neurotoxins were similar to the properties of the original nerve or muscle membranes. In addition to scorpion toxins, a variety of other specific neurotoxins bind to the purified channels and inhibit their activities. These include tetrodotoxin (a poison obtained from... 

Neurotoxins of scorpions especially represent ion channel toxins that mainly affect sodium and potassium channels. Several compounds represent neurotoxins that are directed selectively against insects.97 Na+ channel-specific a-, (3-, and 7-toxins are composed of 58-76 amino acids and contain four stabilizing disulfide bridges.98 The well-studied K+ channel-specific toxins (divided into at least nine distinct peptide subfamilies) bind to the extracellular face of the channel and comprise 29-39 amino acids stabilized by 3-4 disulfide bridges.99 Various Ca2+ channel scorpion toxins, antimicrobial peptides, and short insectotoxins active on Cl channels have been found.96... 

Rogers JC, Qu Y, Tanada TN, Scheuer T, CatteraU WA 1996 Molecular determinants of high affinity binding of a-scorpion toxin and sea anemone toxin in the S3-S4 extraceUular loop in domain IV of the Na channel a subunit. J Biol Chem 271 15950-15962... 

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