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Volume 1, Issue 1
  • ISSN: 2666-1217
  • E-ISSN: 2666-1225

Abstract

The scorpion toxins are the largest potassium channel-blocking, peptide family. The understanding of toxin binding interfaces is usually restricted to two classical binding interfaces: one is the toxin α-helix motif, and the other is the antiparallel β-sheet motif. In this review, such traditional knowledge has been updated by another two different binding interfaces: one is BmKTX toxin using the turn motif between the α-helix and antiparallel β-sheet domains as the binding interface, while the other is Tsκ toxin using the turn motif between the β-sheet in the N-terminal and α-helix domains as the binding interface. Their interaction analysis indicated that the scarce, negatively charged residues in the scorpion toxins played a critical role in orientating the toxin binding interface. In view of the toxin, being negatively charged amino acids as a “binding interface regulator”, the law of scorpion toxin-potassium channel interaction was proposed, that is, the polymorphism of negatively charged residue distribution determines the diversity of toxin binding interfaces. Such a law was used to develop the scorpion toxin-potassium channel recognition control technique. According to this technique, three Kv1.3 channel-targeted peptides, using BmKTX as the template, were designed with the distinct binding interfaces from that of BmKTX by modulating the distribution of toxin, negatively charged residues. In view of the potassium channel as the common target of different animal toxins, the proposed law was also shown to adjust the binding interfaces of other animal toxins. The toxin-potassium channel interaction law would strongly accelerate the research and development of different potassium channel-blocking animal toxins in the future.

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2021-03-01
2024-11-22

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References

  1. WaddingtonJ. RudkinD.M. DunlopJ.A. A new mid-Silurian aquatic scorpion-one step closer to land?Biol. Lett.20151112014081510.1098/rsbl.2014.0815 25589484
     [Google Scholar]
  2. DunlopJ.A.T.O. PrendiniL. Reinterpretation of the Silurian scorpion Proscorpius osborni (Whitfield): Integrating data from Palaeozoic and recent scorpions.Palaeontology20085130332010.1111/j.1475‑4983.2007.00749.x
     [Google Scholar]
  3. Dieter WalossekC.L. Carsten Brauckmann. A scorpion from the Upper Devonian of Hubei Province, China Arachnida, Scorpionida.Neues Jahrbuch fuer Geologie und Palaeontologie1990316918010.1127/njgpm/1990/1990/169
     [Google Scholar]
  4. DiZ.Y. YangZ.Z. YinS.J. CaoZ.J. LiW.X. History of study, updated checklist, distribution and key of scorpions (Arachnida: Scorpiones) from China.Zool. Res.2014351319 24470450
     [Google Scholar]
  5. FroyO. GurevitzM. Arthropod defensins illuminate the divergence of scorpion neurotoxins.J. Pept. Sci.2004101271471810.1002/psc.578 15635623
     [Google Scholar]
  6. CociancichS. GoyffonM. BontemsF. Purification and characterization of a scorpion defensin, a 4kDa antibacterial peptide presenting structural similarities with insect defensins and scorpion toxins.Biochem. Biophys. Res. Commun.19931941172210.1006/bbrc.1993.1778 8333834
     [Google Scholar]
  7. MengL. ZhaoY. QuD. Ion channel modulation by scorpion hemolymph and its defensin ingredients highlights origin of neurotoxins in telson formed in Paleozoic scorpions.Int. J. Biol. Macromol.202014835136310.1016/j.ijbiomac.2020.01.133 31954123
     [Google Scholar]
  8. MengL. XieZ. ZhangQ. Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin.J. Biol. Chem.2016291137097710610.1074/jbc.M115.680611 26817841
     [Google Scholar]
  9. AmemiyaC.T. AlföldiJ. LeeA.P. The African coelacanth genome provides insights into tetrapod evolution.Nature2013496744531131610.1038/nature12027 23598338
     [Google Scholar]
  10. StockerM. Ca(2+)-activated K+ channels: molecular determinants and function of the SK family.Nat. Rev. Neurosci.200451075877010.1038/nrn1516 15378036
     [Google Scholar]
  11. Domingos PossaniL. MartinB.M. SvendsenI. The primary structure of noxiustoxin: A K+ channel blocking peptide, purified from the venom of the scorpion Centruroides noxius Hoffmann.Carlsberg Res. Commun.198247528528910.1007/BF02907789
     [Google Scholar]
  12. CarboneE. WankeE. PrestipinoG. PossaniL.D. MaelickeA. Selective blockage of voltage-dependent K+ channels by a novel scorpion toxin.Nature19822965852909110.1038/296090a0 6278313
     [Google Scholar]
  13. Rodríguez de la VegaR.C. PossaniL.D. Current views on scorpion toxins specific for K+-channels.Toxicon200443886587510.1016/j.toxicon.2004.03.022 15208019
     [Google Scholar]
  14. CaoZ. YuY. WuY. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods.Nat. Commun.20134260210.1038/ncomms3602 24129506
     [Google Scholar]
  15. ChagotB. PimentelC. DaiL. An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis.Biochem. J.2005388Pt 126327110.1042/BJ20041705 15631621
     [Google Scholar]
  16. BontemsF. GilquinB. RoumestandC. MénezA. TomaF. Analysis of side-chain organization on a refined model of charybdotoxin: structural and functional implications.Biochemistry199231347756776410.1021/bi00149a003 1380828
     [Google Scholar]
  17. ChenX. WangQ. NiF. MaJ. Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement.Proc. Natl. Acad. Sci. USA201010725113521135710.1073/pnas.1000142107 20534430
     [Google Scholar]
  18. BanerjeeA. LeeA. CampbellE. MackinnonR. Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel.eLife20132e0059410.7554/eLife.00594 23705070
     [Google Scholar]
  19. ZhaoY. ChenZ. CaoZ. LiW. WuY. Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes.Molecules20192411204510.3390/molecules24112045 31146335
     [Google Scholar]
  20. ChenZ. HuY. HuJ. Unusual binding mode of scorpion toxin BmKTX onto potassium channels relies on its distribution of acidic residues.Biochem. Biophys. Res. Commun.20144471707610.1016/j.bbrc.2014.03.101 24704423
     [Google Scholar]
  21. AugusteP. HuguesM. MourreC. MoinierD. TartarA. LazdunskiM. Scyllatoxin, a blocker of Ca(2+)-activated K+ channels: structure-function relationships and brain localization of the binding sites.Biochemistry199231364865410.1021/bi00118a003 1731919
     [Google Scholar]
  22. Romi-LebrunR. LebrunB. Martin-EauclaireM.F. Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.Biochemistry19973644134731348210.1021/bi971044w 9354615
     [Google Scholar]
  23. RenisioJ.G. Romi-LebrunR. BlancE. BornetO. NakajimaT. DarbonH. Solution structure of BmKTX, a K+ blocker toxin from the Chinese scorpion Buthus Martensi.Proteins2000381707810.1002/(SICI)1097‑0134(20000101)38:1<70:AID‑PROT8>3.0.CO;2‑5 10651040
     [Google Scholar]
  24. HanS. YiH. YinS.J. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease.J. Biol. Chem.200828327190581906510.1074/jbc.M802054200 18480054
     [Google Scholar]
  25. BlancE. LecomteC. RietschotenJ.V. SabatierJ.M. DarbonH. Solution structure of TsKapa, a charybdotoxin-like scorpion toxin from Tityus serrulatus with high affinity for apamin-sensitive Ca(2+)-activated K+ channels.Proteins199729335936910.1002/(SICI)1097‑0134(199711)29:3<359:AID‑PROT9>3.0.CO;2‑5 9365990
     [Google Scholar]
  26. LecomteC. FerratG. FajlounZ. Chemical synthesis and structure-activity relationships of Ts kappa, a novel scorpion toxin acting on apamin-sensitive SK channel.J. Pept. Res.199954536937610.1034/j.1399‑3011.1999.00107.x 10563502
     [Google Scholar]
  27. HanS. YinS. YiH. Protein-protein recognition control by modulating electrostatic interactions.J. Proteome Res.2010963118312510.1021/pr100027k 20405930
     [Google Scholar]
  28. ShenB. CaoZ. LiW. SabatierJ.M. WuY. Treating autoimmune disorders with venom-derived peptides.Expert Opin. Biol. Ther.20171791065107510.1080/14712598.2017.1346606 28695745
     [Google Scholar]
  29. LiZ. LiuW.H. HanS. Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model.J. Biol. Chem.201228735294792949410.1074/jbc.M112.379594 22761436
     [Google Scholar]
  30. ChenZ. HuY. HongJ. Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel.Sci. Rep.20155988110.1038/srep09881 25955787
     [Google Scholar]
  31. AdamsD.J. LewisR.J. Neuropharmacology of venom peptides.Neuropharmacology20171271310.1016/j.neuropharm.2017.11.025 29154773
     [Google Scholar]
  32. HuguesM. RomeyG. DuvalD. VincentJ.P. LazdunskiM. Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor.Proc. Natl. Acad. Sci. USA19827941308131210.1073/pnas.79.4.1308 6122211
     [Google Scholar]
  33. Labbé-JulliéC. GranierC. AlbericioF. Binding and toxicity of apamin. Characterization of the active site.Eur. J. Biochem.1991196363964510.1111/j.1432‑1033.1991.tb15860.x 2013287
     [Google Scholar]
  34. ShonK.J. StockerM. TerlauH. kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel.J. Biol. Chem.19982731333810.1074/jbc.273.1.33 9417043
     [Google Scholar]
  35. JacobsenR.B. KochE.D. Lange-MaleckiB. Single amino acid substitutions in kappa-conotoxin PVIIA disrupt interaction with the shaker K+ channel.J. Biol. Chem.200027532246392464410.1074/jbc.C900990199 10818087
     [Google Scholar]
  36. PenningtonM.W. ByrnesM.E. ZaydenbergI. Chemical synthesis and characterization of ShK toxin: a potent potassium channel inhibitor from a sea anemone.Int. J. Pept. Protein Res.199546535435810.1111/j.1399‑3011.1995.tb01068.x 8567178
     [Google Scholar]
  37. KalmanK. PenningtonM.W. LaniganM.D. ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide.J. Biol. Chem.199827349326973270710.1074/jbc.273.49.32697 9830012
     [Google Scholar]
/content/journals/vat/10.2174/2666121701999200531143349
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Scorpion Toxin-potassium Channel Interaction Law and its Applications
Ven and Tox 1, 15 (2021); https://doi.org/10.2174/2666121701999200531143349
/content/journals/vat/10.2174/2666121701999200531143349
/content/journals/vat/10.2174/2666121701999200531143349
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  • Article Type:     Review Article
Keyword(s): bee toxin; binding interface; interaction law; peptide drug design; Scorpion toxin; scorpion toxin-potassium channel recognition control technique; sea anemone toxin; snail toxin

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