A scorpion toxins

Thomsen WJ, Catterall WA. Localization of the receptor site for a-scorpion toxins by antibody mapping implications for sodium channel topology. Proc Natl Acad Sci USA 1989 86 10161-10165. 

Figure 30-16 Structures of some neurotoxins that affect ion channels. Other neurotoxins include the Na+, K+-ATPase inhibitor ouabain (Fig. 22-12), batrachotoxin (Fig. 22-12), and picrotoxin (Fig. 22-4). The structure of a scorpion toxin is from Almassy et al.,i9ia that of to conotoxin is from Pallaghy et al.,i35 and that of brevetoxin is redrawn after Shimizu et al.i36...

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... 

Isom A while ago, we had the idea that the binding site for a scorpion toxin was the site of interaction between /il and a. Do you still think that is true ... 

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. 

Goldin The model for the a scorpion toxins is that they prevent the domain IV S4 helix from moving out a little bit. If this is true, either you should see a slowing of activation, or domain IV S4 doesn t have to move to open the channel. 

Binding site 3 I S5-IS6, IV S3-S4 IV S5-S6 II S1-S2, II S3-S4 a-scorpion toxins Sea anemone toxins p-scorpion toxins Delayed inactivation... 

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