Scorpion toxins are proteins found in the venom of scorpions. Their toxic effect may be mammal- or insect-specific and acts by binding with varying degrees of specificity to members of the Voltage-gated ion channel superfamily; specifically, voltage-gated sodium channels, voltage-gated potassium channels,[3] and Transient Receptor Potential (TRP) channels.[4][5] The result of this action is to activate or inhibit the action of these channels in the nervous and cardiac organ systems. For instance, α-scorpion toxins MeuNaTxα-12 and MeuNaTxα-13 from Mesobuthus eupeus are neurotoxins that target voltage-gated Na+ channels (Navs), inhibiting fast inactivation. In vivo assays of MeuNaTxα-12 and MeuNaTxα-13 effects on mammalian and insect Navs show differential potency. These recombinants (MeuNaTxα-12 and MeuNaTxα-13) exhibit their preferential affinity for mammalian and insect Na+ channels at the α-like toxins' active site, site 3, in order to inactivate the cell membrane depolarization faster[6]. The varying sensitivity of different Navs to MeuNaTxα-12 and MeuNaTxα-13 may be dependent on the substitution of a conserved Valine residue for a Phenylalanine residue at position 1630 of the LD4:S3-S4 subunit or due to various changes in residues in the LD4:S5-S6 subunit of the Navs.[6] Ultimately, these actions can serve the purpose of warding off predators by causing pain (e.g., through the activation of sodium channels or TRP channels in sensory neurons)[7] or to subdue predators (e.g., in the case of inhibition of cardiac ion channels).[8]
Scorpion long-chain toxin
Crystal structure of toxin II from the scorpion Androctonus australis Hector.[1]
The complete covalent structure of several such toxins has been deduced: They comprise around 66 amino acid residues forming a three stranded anti-parallel beta sheet over which lies an alpha helix of approximately three turns. Four disulfide bridges cross-link the structure of the long-chain toxins whereas the short toxins contain only three.[12][13]BmKAEP, an anti-epilepsy peptide isolated from the venom of the Manchurian scorpion,[14] shows similarity to both scorpion neurotoxins and anti-insect toxins.
Functionedit
The toxin's molecular function is to inhibit ion channels. The two types of Na+ channel toxins can be divided into two groups (alpha and beta) based on their functional effects. Beta (β) toxins shift the voltage-dependence of activation to more negative potentials, making the channel more likely to open at membrane potentials where activation would normally not occur. Alpha (α) toxins inhibit the fast inactivation mechanism, prolonging Na+ current through the channel.[15] The toxins are used in insecticides, vaccines, and protein engineering scaffolds[citation needed]. The toxins are now used to treat cancer patients by injecting fluorescent scorpion toxin into cancerous tissue to show tumor boundaries[citation needed]. Scorpion toxin genes are also used to kill insect pests by creating hypervirulent fungus in the insect through gene insertion[citation needed].
^PDB: 1PTX; Housset D, Habersetzer-Rochat C, Astier JP, Fontecilla-Camps JC (April 1994). "Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution". Journal of Molecular Biology. 238 (1): 88–103. doi:10.1006/jmbi.1994.1270. PMID 8145259.
^Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G (August 1995). "Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry". Protein Science. 4 (8): 1478–89. doi:10.1002/pro.5560040805. PMC2143198. PMID 8520473.
^Miller C (July 1995). "The charybdotoxin family of K+ channel-blocking peptides". Neuron. 15 (1): 5–10. doi:10.1016/0896-6273(95)90057-8. PMID 7542463. S2CID 5256644.
^Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, et al. (June 2016). "Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain". Nature. 534 (7608): 494–9. Bibcode:2016Natur.534..494O. doi:10.1038/nature17976. PMC4919188. PMID 27281198.
^Lin King JV, Emrick JJ, Kelly MJ, Herzig V, King GF, Medzihradszky KF, Julius D (September 2019). "A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain". Cell. 178 (6): 1362–1374.e16. doi:10.1016/j.cell.2019.07.014. PMC6731142. PMID 31447178.
^Zhu L, Peigneur S, Gao B, Tytgat J, Zhu S (September 2013). "Two recombinant α-like scorpion toxins from Mesobuthus eupeus with differential affinity toward insect and mammalian Na(+) channels". Biochimie. 95 (9): 1732–40. doi:10.1016/j.biochi.2013.05.009. PMID 23743216.
^Bohlen CJ, Julius D (September 2012). "Receptor-targeting mechanisms of pain-causing toxins: How ow?". Toxicon. 60 (3): 254–64. doi:10.1016/j.toxicon.2012.04.336. PMC3383939. PMID 22538196.
^Kalia J, Milescu M, Salvatierra J, Wagner J, Klint JK, King GF, et al. (January 2015). "From foe to friend: using animal toxins to investigate ion channel function". Journal of Molecular Biology. 427 (1): 158–175. doi:10.1016/j.jmb.2014.07.027. PMC4277912. PMID 25088688.
^Ceciliani F, Bortolotti F, Menegatti E, Ronchi S, Ascenzi P, Palmieri S (April 1994). "Purification, inhibitory properties, amino acid sequence and identification of the reactive site of a new serine proteinase inhibitor from oil-rape (Brassica napus) seed". FEBS Letters. 342 (2): 221–4. doi:10.1016/0014-5793(94)80505-9. hdl:2434/208504. PMID 8143882. S2CID 42407931.
^Menegatti E, Tedeschi G, Ronchi S, Bortolotti F, Ascenzi P, Thomas RM, et al. (April 1992). "Purification, inhibitory properties and amino acid sequence of a new serine proteinase inhibitor from white mustard (Sinapis alba L.) seed". FEBS Letters. 301 (1): 10–4. doi:10.1016/0014-5793(92)80199-Q. PMID 1451776.
^Rawlings ND, Tolle DP, Barrett AJ (March 2004). "Evolutionary families of peptidase inhibitors". The Biochemical Journal. 378 (Pt 3): 705–16. doi:10.1042/BJ20031825. PMC1224039. PMID 14705960.
^Kopeyan C, Mansuelle P, Sampieri F, Brando T, Bahraoui EM, Rochat H, Granier C (February 1990). "Primary structure of scorpion anti-insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus". FEBS Letters. 261 (2): 423–6. doi:10.1016/0014-5793(90)80607-K. PMID 2311768. S2CID 40564285.
^Gregoire J, Rochat H (1983). "Covalent structure of toxins I and II from the scorpion Buthus occitanus tunetanus". Toxicon. 21 (1): 153–62. doi:10.1016/0041-0101(83)90058-2. PMID 6845379.
^Zhou XH, Yang D, Zhang JH, Liu CM, Lei KJ (January 1989). "Purification and N-terminal partial sequence of anti-epilepsy peptide from venom of the scorpion Buthus martensii Karsch". The Biochemical Journal. 257 (2): 509–17. doi:10.1042/bj2570509. PMC1135608. PMID 2930463.
^Rowe AH, Xiao Y, Scales J, Linse KD, Rowe MP, Cummins TR, et al. (2011) Isolation and Characterization of CvIV4: A Pain Inducing α- Scorpion Toxin. PLoS ONE 6(8): e23520. https://doi.org/10.1371/journal.pone.0023520
Science News: Scorpion Toxin Tells an Evolutionary Tale
This article incorporates text from the public domain Pfam and InterPro: IPR002061
April 12, 2024
scorpion, toxin, proteins, found, venom, scorpions, their, toxic, effect, mammal, insect, specific, acts, binding, with, varying, degrees, specificity, members, voltage, gated, channel, superfamily, specifically, voltage, gated, sodium, channels, voltage, gate. Scorpion toxins are proteins found in the venom of scorpions Their toxic effect may be mammal or insect specific and acts by binding with varying degrees of specificity to members of the Voltage gated ion channel superfamily specifically voltage gated sodium channels voltage gated potassium channels 3 and Transient Receptor Potential TRP channels 4 5 The result of this action is to activate or inhibit the action of these channels in the nervous and cardiac organ systems For instance a scorpion toxins MeuNaTxa 12 and MeuNaTxa 13 from Mesobuthus eupeus are neurotoxins that target voltage gated Na channels Navs inhibiting fast inactivation In vivo assays of MeuNaTxa 12 and MeuNaTxa 13 effects on mammalian and insect Navs show differential potency These recombinants MeuNaTxa 12 and MeuNaTxa 13 exhibit their preferential affinity for mammalian and insect Na channels at the a like toxins active site site 3 in order to inactivate the cell membrane depolarization faster 6 The varying sensitivity of different Navs to MeuNaTxa 12 and MeuNaTxa 13 may be dependent on the substitution of a conserved Valine residue for a Phenylalanine residue at position 1630 of the LD4 S3 S4 subunit or due to various changes in residues in the LD4 S5 S6 subunit of the Navs 6 Ultimately these actions can serve the purpose of warding off predators by causing pain e g through the activation of sodium channels or TRP channels in sensory neurons 7 or to subdue predators e g in the case of inhibition of cardiac ion channels 8 Scorpion long chain toxinCrystal structure of toxin II from the scorpion Androctonus australis Hector 1 IdentifiersSymbolToxin 3PfamPF00537InterProIPR002061SCOP22sn3 SCOPe SUPFAMTCDB8 B 1OPM superfamily58OPM protein1djtAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryScorpion short toxinAgitoxin 2 Disulphide bonds are highlighted PDB 1agt 2 IdentifiersSymbolToxin 2PfamPF00451Pfam clanCL0054InterProIPR001947PROSITEPDOC00875TCDB8 B 2OPM superfamily58OPM protein1ne5Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryThe family includes related short and long chain scorpion toxins It also contains a group of proteinase inhibitors from the plants Arabidopsis thaliana and Brassica spp The Brassica napus oil seed rape and Sinapis alba white mustard inhibitors 9 10 inhibit the catalytic activity of bovine beta trypsin and bovine alpha chymotrypsin which belong to MEROPS peptidase family S1 InterPro IPR001254 11 This group of proteins is now used in the creation of insecticides vaccines and protein engineering scaffolds Contents 1 Structure 2 Function 3 Subfamilies 4 References 5 External linksStructure editThe complete covalent structure of several such toxins has been deduced They comprise around 66 amino acid residues forming a three stranded anti parallel beta sheet over which lies an alpha helix of approximately three turns Four disulfide bridges cross link the structure of the long chain toxins whereas the short toxins contain only three 12 13 BmKAEP an anti epilepsy peptide isolated from the venom of the Manchurian scorpion 14 shows similarity to both scorpion neurotoxins and anti insect toxins Function editThe toxin s molecular function is to inhibit ion channels The two types of Na channel toxins can be divided into two groups alpha and beta based on their functional effects Beta b toxins shift the voltage dependence of activation to more negative potentials making the channel more likely to open at membrane potentials where activation would normally not occur Alpha a toxins inhibit the fast inactivation mechanism prolonging Na current through the channel 15 The toxins are used in insecticides vaccines and protein engineering scaffolds citation needed The toxins are now used to treat cancer patients by injecting fluorescent scorpion toxin into cancerous tissue to show tumor boundaries citation needed Scorpion toxin genes are also used to kill insect pests by creating hypervirulent fungus in the insect through gene insertion citation needed Subfamilies editNeurotoxin InterPro IPR001219References edit PDB 1PTX Housset D Habersetzer Rochat C Astier JP Fontecilla Camps JC April 1994 Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1 3 A resolution Journal of Molecular Biology 238 1 88 103 doi 10 1006 jmbi 1994 1270 PMID 8145259 Krezel AM Kasibhatla C Hidalgo P MacKinnon R Wagner G August 1995 Solution structure of the potassium channel inhibitor agitoxin 2 caliper for probing channel geometry Protein Science 4 8 1478 89 doi 10 1002 pro 5560040805 PMC 2143198 PMID 8520473 Miller C July 1995 The charybdotoxin family of K channel blocking peptides Neuron 15 1 5 10 doi 10 1016 0896 6273 95 90057 8 PMID 7542463 S2CID 5256644 Osteen JD Herzig V Gilchrist J Emrick JJ Zhang C Wang X et al June 2016 Selective spider toxins reveal a role for the Nav1 1 channel in mechanical pain Nature 534 7608 494 9 Bibcode 2016Natur 534 494O doi 10 1038 nature17976 PMC 4919188 PMID 27281198 Lin King JV Emrick JJ Kelly MJ Herzig V King GF Medzihradszky KF Julius D September 2019 A Cell Penetrating Scorpion Toxin Enables Mode Specific Modulation of TRPA1 and Pain Cell 178 6 1362 1374 e16 doi 10 1016 j cell 2019 07 014 PMC 6731142 PMID 31447178 Zhu L Peigneur S Gao B Tytgat J Zhu S September 2013 Two recombinant a like scorpion toxins from Mesobuthus eupeus with differential affinity toward insect and mammalian Na channels Biochimie 95 9 1732 40 doi 10 1016 j biochi 2013 05 009 PMID 23743216 Bohlen CJ Julius D September 2012 Receptor targeting mechanisms of pain causing toxins How ow Toxicon 60 3 254 64 doi 10 1016 j toxicon 2012 04 336 PMC 3383939 PMID 22538196 Kalia J Milescu M Salvatierra J Wagner J Klint JK King GF et al January 2015 From foe to friend using animal toxins to investigate ion channel function Journal of Molecular Biology 427 1 158 175 doi 10 1016 j jmb 2014 07 027 PMC 4277912 PMID 25088688 Ceciliani F Bortolotti F Menegatti E Ronchi S Ascenzi P Palmieri S April 1994 Purification inhibitory properties amino acid sequence and identification of the reactive site of a new serine proteinase inhibitor from oil rape Brassica napus seed FEBS Letters 342 2 221 4 doi 10 1016 0014 5793 94 80505 9 hdl 2434 208504 PMID 8143882 S2CID 42407931 Menegatti E Tedeschi G Ronchi S Bortolotti F Ascenzi P Thomas RM et al April 1992 Purification inhibitory properties and amino acid sequence of a new serine proteinase inhibitor from white mustard Sinapis alba L seed FEBS Letters 301 1 10 4 doi 10 1016 0014 5793 92 80199 Q PMID 1451776 Rawlings ND Tolle DP Barrett AJ March 2004 Evolutionary families of peptidase inhibitors The Biochemical Journal 378 Pt 3 705 16 doi 10 1042 BJ20031825 PMC 1224039 PMID 14705960 Kopeyan C Mansuelle P Sampieri F Brando T Bahraoui EM Rochat H Granier C February 1990 Primary structure of scorpion anti insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus FEBS Letters 261 2 423 6 doi 10 1016 0014 5793 90 80607 K PMID 2311768 S2CID 40564285 Gregoire J Rochat H 1983 Covalent structure of toxins I and II from the scorpion Buthus occitanus tunetanus Toxicon 21 1 153 62 doi 10 1016 0041 0101 83 90058 2 PMID 6845379 Zhou XH Yang D Zhang JH Liu CM Lei KJ January 1989 Purification and N terminal partial sequence of anti epilepsy peptide from venom of the scorpion Buthus martensii Karsch The Biochemical Journal 257 2 509 17 doi 10 1042 bj2570509 PMC 1135608 PMID 2930463 Rowe AH Xiao Y Scales J Linse KD Rowe MP Cummins TR et al 2011 Isolation and Characterization of CvIV4 A Pain Inducing a Scorpion Toxin PLoS ONE 6 8 e23520 https doi org 10 1371 journal pone 0023520External links editScorpion short toxins in PROSITE Science News Scorpion Toxin Tells an Evolutionary TaleThis article incorporates text from the public domain Pfam and InterPro IPR002061 Retrieved from https en wikipedia org w index php title Scorpion toxin amp oldid 1148120507, wikipedia, wiki, book, books, library,
