| Scorpion long-chain toxin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal structure of toxin II from the scorpion Androctonus australis Hector.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | Toxin_3 | ||||||||
| Pfam | PF00537 | ||||||||
| InterPro | IPR002061 | ||||||||
| SCOP2 | 2sn3 / SCOPe / SUPFAM | ||||||||
| TCDB | 8.B.1 | ||||||||
| OPM superfamily | 58 | ||||||||
| OPM protein | 1djt | ||||||||
| |||||||||
| Scorpion short toxin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| Symbol | Toxin_2 | ||||||||
| Pfam | PF00451 | ||||||||
| Pfam clan | CL0054 | ||||||||
| InterPro | IPR001947 | ||||||||
| PROSITE | PDOC00875 | ||||||||
| TCDB | 8.B.2 | ||||||||
| OPM superfamily | 58 | ||||||||
| OPM protein | 1ne5 | ||||||||
| |||||||||
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]
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,[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.
- ^ 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 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. 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.