Scorpion toxin

{{Pfam_box

| Symbol = Toxin_3

| Name = Scorpion long-chain toxin

| image =scorpiontoxinproteinimage.png

| width =

| caption = Crystal structure of toxin II from the scorpion Androctonus australis Hector.{{PDB|1PTX}}; {{cite journal | vauthors = Housset D, Habersetzer-Rochat C, Astier JP, Fontecilla-Camps JC | title = Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution | journal = Journal of Molecular Biology | volume = 238 | issue = 1 | pages = 88–103 | date = April 1994 | pmid = 8145259 | doi = 10.1006/jmbi.1994.1270 }}

| Pfam= PF00537

| InterPro= IPR002061

| SMART=

| Prosite =

| SCOP = 2sn3

| TCDB = 8.B.1

| OPM family= 58

| OPM protein= 1djt

| PDB=

}}

{{Infobox protein family

| Symbol = Toxin_2

| Name = Scorpion short toxin

| image = 1agt.png

| width =

| caption = Agitoxin-2. Disulphide bonds are highlighted. PDB {{PDBe|1agt}} {{cite journal | vauthors = Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G | title = Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry | journal = Protein Science | volume = 4 | issue = 8 | pages = 1478–89 | date = August 1995 | pmid = 8520473 | pmc = 2143198 | doi = 10.1002/pro.5560040805 }}

| Pfam = PF00451

| Pfam_clan = CL0054

| InterPro = IPR001947

| SMART =

| PROSITE = PDOC00875

| MEROPS =

| SCOP =

| TCDB = 8.B.2

| OPM family = 58

| OPM protein = 1ne5

| CAZy =

| CDD =

}}

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,{{cite journal | vauthors = Miller C | s2cid = 5256644 | title = The charybdotoxin family of K+ channel-blocking peptides | journal = Neuron | volume = 15 | issue = 1 | pages = 5–10 | date = July 1995 | pmid = 7542463 | doi = 10.1016/0896-6273(95)90057-8 | doi-access = free }} and Transient Receptor Potential (TRP) channels.{{cite journal | vauthors = Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EA, Alewood P, Stucky CL, Brierley SM, Basbaum AI, Bosmans F, King GF, Julius D | display-authors = 6 | title = Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain | journal = Nature | volume = 534 | issue = 7608 | pages = 494–9 | date = June 2016 | pmid = 27281198 | pmc = 4919188 | doi = 10.1038/nature17976 | bibcode = 2016Natur.534..494O }}{{cite journal | vauthors = Lin King JV, Emrick JJ, Kelly MJ, Herzig V, King GF, Medzihradszky KF, Julius D | title = A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain | journal = Cell | volume = 178 | issue = 6 | pages = 1362–1374.e16 | date = September 2019 | pmid = 31447178 | pmc = 6731142 | doi = 10.1016/j.cell.2019.07.014 }} 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 (Na_vs), inhibiting fast inactivation. In vivo assays of MeuNaTxα-12 and MeuNaTxα-13 effects on mammalian and insect Na_vs 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 Na_vs 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 Na_vs.{{cite journal | vauthors = Zhu L, Peigneur S, Gao B, Tytgat J, Zhu S | title = Two recombinant α-like scorpion toxins from Mesobuthus eupeus with differential affinity toward insect and mammalian Na(+) channels | journal = Biochimie | volume = 95 | issue = 9 | pages = 1732–40 | date = September 2013 | pmid = 23743216 | doi = 10.1016/j.biochi.2013.05.009 }} 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){{cite journal | vauthors = Bohlen CJ, Julius D | title = Receptor-targeting mechanisms of pain-causing toxins: How ow? | journal = Toxicon | volume = 60 | issue = 3 | pages = 254–64 | date = September 2012 | pmid = 22538196 | pmc = 3383939 | doi = 10.1016/j.toxicon.2012.04.336 }} or to subdue predators (e.g., in the case of inhibition of cardiac ion channels).{{cite journal | vauthors = Kalia J, Milescu M, Salvatierra J, Wagner J, Klint JK, King GF, Olivera BM, Bosmans F | display-authors = 6 | title = From foe to friend: using animal toxins to investigate ion channel function | journal = Journal of Molecular Biology | volume = 427 | issue = 1 | pages = 158–175 | date = January 2015 | pmid = 25088688 | pmc = 4277912 | doi = 10.1016/j.jmb.2014.07.027 }}

The 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,{{cite journal | vauthors = Ceciliani F, Bortolotti F, Menegatti E, Ronchi S, Ascenzi P, Palmieri S | title = Purification, inhibitory properties, amino acid sequence and identification of the reactive site of a new serine proteinase inhibitor from oil-rape (Brassica napus) seed | journal = FEBS Letters | volume = 342 | issue = 2 | pages = 221–4 | date = April 1994 | pmid = 8143882 | doi = 10.1016/0014-5793(94)80505-9 | hdl-access = free | hdl = 2434/208504 | s2cid = 42407931 }}{{cite journal | vauthors = Menegatti E, Tedeschi G, Ronchi S, Bortolotti F, Ascenzi P, Thomas RM, Bolognesi M, Palmieri S | display-authors = 6 | title = Purification, inhibitory properties and amino acid sequence of a new serine proteinase inhibitor from white mustard (Sinapis alba L.) seed | journal = FEBS Letters | volume = 301 | issue = 1 | pages = 10–4 | date = April 1992 | pmid = 1451776 | doi = 10.1016/0014-5793(92)80199-Q | doi-access = free }} inhibit the catalytic activity of bovine beta-trypsin and bovine alpha-chymotrypsin, which belong to MEROPS peptidase family S1 ({{InterPro|IPR001254}}).{{cite journal | vauthors = Rawlings ND, Tolle DP, Barrett AJ | title = Evolutionary families of peptidase inhibitors | journal = The Biochemical Journal | volume = 378 | issue = Pt 3 | pages = 705–16 | date = March 2004 | pmid = 14705960 | pmc = 1224039 | doi = 10.1042/BJ20031825 }}

This group of proteins is now used in the creation of insecticides, vaccines, and protein engineering scaffolds.