1wz5
Solution structure of Pi1-3p
Structural highlights
FunctionKAX61_PANIM Potently and reversibly inhibits the insect voltage-gated Shaker (Sh) potassium channel (isoform alpha (B)), the mammalian voltage-gated potassium channels Kv1.2/KCNA2. Its effect on Kv1.3/KCNA3 is controversial, since this channel is voltage-independently inhibited in PubMed:9464266, but is not affected in PubMed:10931199. Furthermore, this toxin competes with apamin (a small conductance calcium-activated potassium channel inhibitor) for binding onto rat brain synaptosomes.[1] [2] [3] [4] Publication Abstract from PubMedAnimal toxins are highly reticulated and structured polypeptides that adopt a limited number of folds. In scorpion species, the most represented fold is the alpha/beta scaffold in which an helical structure is connected to an antiparallel beta-sheet by two disulfide bridges. The intimate relationship existing between peptide reticulation and folding remains poorly understood. Here, we investigated the role of disulfide bridging on the 3D structure of HsTx1, a scorpion toxin potently active on Kv1.1 and Kv1.3 channels. This toxin folds along the classical alpha/beta scaffold but belongs to a unique family of short-chain, four disulfide-bridged toxins. Removal of the fourth disulfide bridge of HsTx1 does not affect its helical structure, whereas its two-stranded beta-sheet is altered from a twisted to a nontwisted configuration. This structural change in HsTx1 is accompanied by a marked decrease in Kv1.1 and Kv1.3 current blockage, and by alterations in the toxin to channel molecular contacts. In contrast, a similar removal of the fourth disulfide bridge of Pi1, another scorpion toxin from the same structural family, has no impact on its 3D structure, pharmacology, or channel interaction. These data highlight the importance of disulfide bridging in reaching the correct bioactive conformation of some toxins. The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily.,Carrega L, Mosbah A, Ferrat G, Beeton C, Andreotti N, Mansuelle P, Darbon H, De Waard M, Sabatier JM Proteins. 2005 Dec 1;61(4):1010-23. PMID:16247791[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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