Login Register Cart 0
Generic placeholder image

Venoms and Toxins

Editor-in-Chief

ISSN (Print): 2666-1217
ISSN (Online): 2666-1225

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Scorpion Toxin-potassium Channel Interaction Law and its Applications

Author(s): Zheng Zuo, Zongyun Chen, Zhijian Cao, Wenxin Li and Yingliang Wu*

Volume 1, Issue 1, 2021

Published on: 31 May, 2020

Page: [15 - 26] Pages: 12

DOI: 10.2174/2666121701999200531143349

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.

Keywords: Scorpion toxin, binding interface, interaction law, scorpion toxin-potassium channel recognition control technique, peptide drug design, bee toxin, sea anemone toxin, snail toxin.

Graphical Abstract

[1]
Waddington J, Rudkin DM, Dunlop JA. A new mid-Silurian aquatic scorpion-one step closer to land? Biol Lett 2015; 11(1)20140815
[http://dx.doi.org/10.1098/rsbl.2014.0815] [PMID: 25589484]
[2]
Dunlop JATO, Prendini L. Reinterpretation of the Silurian scorpion Proscorpius osborni (Whitfield): Integrating data from Palaeozoic and recent scorpions. Palaeontology 2008; 51: 303-20.
[http://dx.doi.org/10.1111/j.1475-4983.2007.00749.x]
[3]
Dieter Walossek CL. Carsten Brauckmann. A scorpion from the Upper Devonian of Hubei Province, China Arachnida, Scorpionida. Neues Jahrbuch fuer Geologie und Palaeontologie 1990; 3: 169-80.
[http://dx.doi.org/10.1127/njgpm/1990/1990/169]
[4]
Di ZY, Yang ZZ, Yin SJ, Cao ZJ, Li WX. History of study, updated checklist, distribution and key of scorpions (Arachnida: Scorpiones) from China. Zool Res 2014; 35(1): 3-19.
[PMID: 24470450]
[5]
Froy O, Gurevitz M. Arthropod defensins illuminate the divergence of scorpion neurotoxins. J Pept Sci 2004; 10(12): 714-8.
[http://dx.doi.org/10.1002/psc.578] [PMID: 15635623]
[6]
Cociancich S, Goyffon M, Bontems F, et al. Purification and characterization of a scorpion defensin, a 4kDa antibacterial peptide presenting structural similarities with insect defensins and scorpion toxins. Biochem Biophys Res Commun 1993; 194(1): 17-22.
[http://dx.doi.org/10.1006/bbrc.1993.1778] [PMID: 8333834]
[7]
Meng L, Zhao Y, Qu D, et al. Ion channel modulation by scorpion hemolymph and its defensin ingredients highlights origin of neurotoxins in telson formed in Paleozoic scorpions. Int J Biol Macromol 2020; 148: 351-63.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.133] [PMID: 31954123]
[8]
Meng L, Xie Z, Zhang Q, et al. Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin. J Biol Chem 2016; 291(13): 7097-106.
[http://dx.doi.org/10.1074/jbc.M115.680611] [PMID: 26817841]
[9]
Amemiya CT, Alföldi J, Lee AP, et al. The African coelacanth genome provides insights into tetrapod evolution. Nature 2013; 496(7445): 311-6.
[http://dx.doi.org/10.1038/nature12027] [PMID: 23598338]
[10]
Stocker M. Ca(2+)-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci 2004; 5(10): 758-70.
[http://dx.doi.org/10.1038/nrn1516] [PMID: 15378036]
[11]
Domingos Possani L, Martin BM, Svendsen I. The primary structure of noxiustoxin: A K+ channel blocking peptide, purified from the venom of the scorpion Centruroides noxius Hoffmann. Carlsberg Res Commun 1982; 47(5): 285-9.
[http://dx.doi.org/10.1007/BF02907789]
[12]
Carbone E, Wanke E, Prestipino G, Possani LD, Maelicke A. Selective blockage of voltage-dependent K+ channels by a novel scorpion toxin. Nature 1982; 296(5852): 90-1.
[http://dx.doi.org/10.1038/296090a0] [PMID: 6278313]
[13]
Rodríguez de la Vega RC, Possani LD. Current views on scorpion toxins specific for K+-channels. Toxicon 2004; 43(8): 865-75.
[http://dx.doi.org/10.1016/j.toxicon.2004.03.022] [PMID: 15208019]
[14]
Cao Z, Yu Y, Wu Y, et al. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods. Nat Commun 2013; 4: 2602.
[http://dx.doi.org/10.1038/ncomms3602] [PMID: 24129506]
[15]
Chagot B, Pimentel C, Dai L, et al. An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis. Biochem J 2005; 388(Pt 1): 263-71.
[http://dx.doi.org/10.1042/BJ20041705] [PMID: 15631621]
[16]
Bontems F, Gilquin B, Roumestand C, Ménez A, Toma F. Analysis of side-chain organization on a refined model of charybdotoxin: structural and functional implications. Biochemistry 1992; 31(34): 7756-64.
[http://dx.doi.org/10.1021/bi00149a003] [PMID: 1380828]
[17]
Chen X, Wang Q, Ni F, Ma J. Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement. Proc Natl Acad Sci USA 2010; 107(25): 11352-7.
[http://dx.doi.org/10.1073/pnas.1000142107] [PMID: 20534430]
[18]
Banerjee A, Lee A, Campbell E, Mackinnon R. Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel. eLife 2013; 2e00594
[http://dx.doi.org/10.7554/eLife.00594] [PMID: 23705070]
[19]
Zhao Y, Chen Z, Cao Z, Li W, Wu Y. Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes. Molecules 2019; 24(11): 2045.
[http://dx.doi.org/10.3390/molecules24112045] [PMID: 31146335]
[20]
Chen Z, Hu Y, Hu J, et al. Unusual binding mode of scorpion toxin BmKTX onto potassium channels relies on its distribution of acidic residues. Biochem Biophys Res Commun 2014; 447(1): 70-6.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.101] [PMID: 24704423]
[21]
Auguste P, Hugues M, Mourre C, Moinier D, Tartar A, Lazdunski M. Scyllatoxin, a blocker of Ca(2+)-activated K+ channels: structure-function relationships and brain localization of the binding sites. Biochemistry 1992; 31(3): 648-54.
[http://dx.doi.org/10.1021/bi00118a003] [PMID: 1731919]
[22]
Romi-Lebrun R, Lebrun B, Martin-Eauclaire MF, et al. Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels. Biochemistry 1997; 36(44): 13473-82.
[http://dx.doi.org/10.1021/bi971044w] [PMID: 9354615]
[23]
Renisio JG, Romi-Lebrun R, Blanc E, Bornet O, Nakajima T, Darbon H. Solution structure of BmKTX, a K+ blocker toxin from the Chinese scorpion Buthus Martensi. Proteins 2000; 38(1): 70-8.
[http://dx.doi.org/10.1002/(SICI)1097-0134(20000101)38:1<70:AID-PROT8>3.0.CO;2-5] [PMID: 10651040]
[24]
Han S, Yi H, Yin SJ, et al. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease. J Biol Chem 2008; 283(27): 19058-65.
[http://dx.doi.org/10.1074/jbc.M802054200] [PMID: 18480054]
[25]
Blanc E, Lecomte C, Rietschoten JV, Sabatier JM, Darbon H. Solution structure of TsKapa, a charybdotoxin-like scorpion toxin from Tityus serrulatus with high affinity for apamin-sensitive Ca(2+)-activated K+ channels. Proteins 1997; 29(3): 359-69.
[http://dx.doi.org/10.1002/(SICI)1097-0134(199711)29:3<359:AID-PROT9>3.0.CO;2-5] [PMID: 9365990]
[26]
Lecomte C, Ferrat G, Fajloun Z, et al. Chemical synthesis and structure-activity relationships of Ts kappa, a novel scorpion toxin acting on apamin-sensitive SK channel. J Pept Res 1999; 54(5): 369-76.
[http://dx.doi.org/10.1034/j.1399-3011.1999.00107.x] [PMID: 10563502]
[27]
Han S, Yin S, Yi H, et al. Protein-protein recognition control by modulating electrostatic interactions. J Proteome Res 2010; 9(6): 3118-25.
[http://dx.doi.org/10.1021/pr100027k] [PMID: 20405930]
[28]
Shen B, Cao Z, Li W, Sabatier JM, Wu Y. Treating autoimmune disorders with venom-derived peptides. Expert Opin Biol Ther 2017; 17(9): 1065-75.
[http://dx.doi.org/10.1080/14712598.2017.1346606] [PMID: 28695745]
[29]
Li Z, Liu WH, Han S, et al. 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 2012; 287(35): 29479-94.
[http://dx.doi.org/10.1074/jbc.M112.379594] [PMID: 22761436]
[30]
Chen Z, Hu Y, Hong J, et al. Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel. Sci Rep 2015; 5: 9881.
[http://dx.doi.org/10.1038/srep09881] [PMID: 25955787]
[31]
Adams DJ, Lewis RJ. Neuropharmacology of venom peptides. Neuropharmacology 2017; 127: 1-3.
[http://dx.doi.org/10.1016/j.neuropharm.2017.11.025] [PMID: 29154773]
[32]
Hugues M, Romey G, Duval D, Vincent JP, Lazdunski M. 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 USA 1982; 79(4): 1308-12.
[http://dx.doi.org/10.1073/pnas.79.4.1308] [PMID: 6122211]
[33]
Labbé-Jullié C, Granier C, Albericio F, et al. Binding and toxicity of apamin. Characterization of the active site. Eur J Biochem 1991; 196(3): 639-45.
[http://dx.doi.org/10.1111/j.1432-1033.1991.tb15860.x] [PMID: 2013287]
[34]
Shon KJ, Stocker M, Terlau H, et al. kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel. J Biol Chem 1998; 273(1): 33-8.
[http://dx.doi.org/10.1074/jbc.273.1.33] [PMID: 9417043]
[35]
Jacobsen RB, Koch ED, Lange-Malecki B, et al. Single amino acid substitutions in kappa-conotoxin PVIIA disrupt interaction with the shaker K+ channel. J Biol Chem 2000; 275(32): 24639-44.
[http://dx.doi.org/10.1074/jbc.C900990199] [PMID: 10818087]
[36]
Pennington MW, Byrnes ME, Zaydenberg I, et al. Chemical synthesis and characterization of ShK toxin: a potent potassium channel inhibitor from a sea anemone. Int J Pept Protein Res 1995; 46(5): 354-8.
[http://dx.doi.org/10.1111/j.1399-3011.1995.tb01068.x] [PMID: 8567178]
[37]
Kalman K, Pennington MW, Lanigan MD, et al. ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem 1998; 273(49): 32697-707.
[http://dx.doi.org/10.1074/jbc.273.49.32697] [PMID: 9830012]

Rights & Permissions Print Cite
Article Metrics
38
1
© 2024 Bentham Science Publishers | Privacy Policy