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| | ==NMR solution structure of natural scorpion toxin Cl13== | | ==NMR solution structure of natural scorpion toxin Cl13== |
| - | <StructureSection load='6vxw' size='340' side='right'caption='[[6vxw]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6vxw' size='340' side='right'caption='[[6vxw]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vxw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Centruroides_limpidus Centruroides limpidus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VXW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VXW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vxw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Centruroides_limpidus Centruroides limpidus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VXW FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxw OCA], [http://pdbe.org/6vxw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vxw RCSB], [http://www.ebi.ac.uk/pdbsum/6vxw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxw ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxw OCA], [https://pdbe.org/6vxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vxw RCSB], [https://www.ebi.ac.uk/pdbsum/6vxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SCXD_CENLI SCXD_CENLI] Beta toxins bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing (By similarity). Inhibits sodium channels Nav1.4/SCN4A, Nav1.5/SCN5A and Nav1.6/SCN8A (PubMed:27871874). Also has a weak inhibitory effect on Nav1.2/SCN2A (PubMed:27871874). Is lethal to mice (PubMed:27871874).[UniProtKB:P60266]<ref>PMID:27871874</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Centruroides limpidus]] | | [[Category: Centruroides limpidus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Delepierre, M]] | + | [[Category: Delepierre M]] |
| - | [[Category: Giraldo, A E.Lopez]] | + | [[Category: Lopez Giraldo AE]] |
| - | [[Category: Portilla, F del Rio]] | + | [[Category: Del Rio Portilla F]] |
| - | [[Category: Sodium beta toxin]]
| + | |
| - | [[Category: Toxin]]
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| Structural highlights
Function
SCXD_CENLI Beta toxins bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing (By similarity). Inhibits sodium channels Nav1.4/SCN4A, Nav1.5/SCN5A and Nav1.6/SCN8A (PubMed:27871874). Also has a weak inhibitory effect on Nav1.2/SCN2A (PubMed:27871874). Is lethal to mice (PubMed:27871874).[UniProtKB:P60266][1]
Publication Abstract from PubMed
Cl13 is a toxin purified previously from the venom of the Mexican scorpion Centruroides limpidus. This toxin affects the function of voltage gated Na(+)-channels, human subtypes Nav1.4, Nav1.5 and Nav1.6 in a similar manner as other known beta-toxins from scorpion venoms. Here, we report a correction of the primary structure of Cl13, previously published. The peptide does contain 66 amino acids, but residue 58 is a tryptophan and the last C-terminal amino acid is an amidated lysine, instead of arginine. The main contribution of this communication is the determination of the 3D-structure of Cl13, by solution NMR, showing that Cl13 has the classical cysteine-stabilized alpha/beta (CSalpha/beta) folding. It has a triple stranded antiparallel beta sheet commonly present in scorpion sodium channel a-toxins. In addition, we report and discuss a comparison of Cl13 structure with two other toxins (Cn2 and Css2) from scorpions of the same genus Centruroides, which shows important surface similarities with the structure reported here. Finally, the lack of neutralization of Cl13 toxin by two single-chain antibody fragments (scFvs), named LR and 10FG2, which are capable of neutralizing various toxins from Mexican scorpions, is revised. In particular, 10FG2 is capable of neutralizing toxins Cll1 and Cll2 of the same scorpion C. limpidus. The reasons why LR and 10FG2 are unable of neutralizing Cl13 toxin are discussed.
The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus.,Lopez-Giraldo AE, Olamendi-Portugal T, Riano-Umbarila L, Becerril B, Possani LD, Delepierre M, Rio-Portilla FD Toxicon. 2020 Jun 19. pii: S0041-0101(20)30290-7. doi:, 10.1016/j.toxicon.2020.06.011. PMID:32569846[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Olamendi-Portugal T, Restano-Cassulini R, Riaño-Umbarila L, Becerril B, Possani LD. Functional and immuno-reactive characterization of a previously undescribed peptide from the venom of the scorpion Centruroides limpidus. Peptides. 2017 Jan;87:34-40. PMID:27871874 doi:10.1016/j.peptides.2016.11.008
- ↑ Lopez-Giraldo AE, Olamendi-Portugal T, Riano-Umbarila L, Becerril B, Possani LD, Delepierre M, Rio-Portilla FD. The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus. Toxicon. 2020 Jun 19. pii: S0041-0101(20)30290-7. doi:, 10.1016/j.toxicon.2020.06.011. PMID:32569846 doi:http://dx.doi.org/10.1016/j.toxicon.2020.06.011
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