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| | ==LSIII (NMR, 23 STRUCTURES)== | | ==LSIII (NMR, 23 STRUCTURES)== |
| - | <StructureSection load='1lsi' size='340' side='right' caption='[[1lsi]], [[NMR_Ensembles_of_Models | 23 NMR models]]' scene=''> | + | <StructureSection load='1lsi' size='340' side='right'caption='[[1lsi]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1lsi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Black-banded_sea_krait Black-banded sea krait]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LSI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LSI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lsi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Laticauda_semifasciata Laticauda semifasciata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LSI FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lsi OCA], [http://pdbe.org/1lsi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lsi RCSB], [http://www.ebi.ac.uk/pdbsum/1lsi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lsi ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 23 models</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=1lsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lsi OCA], [https://pdbe.org/1lsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lsi RCSB], [https://www.ebi.ac.uk/pdbsum/1lsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lsi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NXL1_PSSEM NXL1_PSSEM]] Binds with high affinity to muscular (alpha-1/CHRNA1) and neuronal (alpha-7/CHRNA7) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission.<ref>PMID:9305882</ref> | + | [https://www.uniprot.org/uniprot/3L21_LATSE 3L21_LATSE] Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=1.6 nM) and neuronal (chimeric alpha-7/CHRNA7, Kd=3 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). Also shows a very weak inhibition on GABA(A) receptors (PubMed:26221036). The toxin (10 uM) inhibits 83% of current in channels composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits, 39% of current in channels composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits, and 33% of current in channels composed of alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:26221036).<ref>PMID:26221036</ref> <ref>PMID:9305882</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ls/1lsi_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ls/1lsi_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Black-banded sea krait]] | + | [[Category: Large Structures]] |
| - | [[Category: Connolly, P J]] | + | [[Category: Laticauda semifasciata]] |
| - | [[Category: Hoch, J C]] | + | [[Category: Connolly PJ]] |
| - | [[Category: Stern, A S]] | + | [[Category: Hoch JC]] |
| - | [[Category: Multigene family]] | + | [[Category: Stern AS]] |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Venom]]
| + | |
| Structural highlights
Function
3L21_LATSE Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=1.6 nM) and neuronal (chimeric alpha-7/CHRNA7, Kd=3 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). Also shows a very weak inhibition on GABA(A) receptors (PubMed:26221036). The toxin (10 uM) inhibits 83% of current in channels composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits, 39% of current in channels composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits, and 33% of current in channels composed of alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:26221036).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We report the sequence-specific proton assignments and solution structure of the long neurotoxin LSIII from the venom of Laticauda semifasciata determined by two- and three-dimensional 1H NMR. Input for structure calculations consisted of 497 NOE-derived distance restraints and 45 dihedral angle restraints obtained from J couplings. A two-particle-per-residue representation of protein structure was used to generate 200 initial structures which were then subjected to all-atom refinement by simulated annealing. Twenty-three final structures consistent with the experimental restraints were obtained; the average atomic RMS difference between the individual structures and the mean structure was 0.82 A for the backbone heavy atoms and 1.3 A for all heavy atoms (residues 1-26, 37-60). The main elements of regular secondary structure are a three-stranded antiparallel beta-sheet and three finger-like loops protruding from a globular core, consistent with previously reported structures of long neurotoxins. The end of the prominent loop II, which is involved in binding to acetylcholine receptor, is disordered relative to the rest of the molecule. A novel finding of this study is that the loop has a well defined local structure; this and other observations suggest this region moves as a rigid body. We propose that this motion is a heretofore unrecognized general feature of long neurotoxins, with specific consequences for binding to the acetylcholine receptor.
Solution structure of LSIII, a long neurotoxin from the venom of Laticauda semifasciata.,Connolly PJ, Stern AS, Hoch JC Biochemistry. 1996 Jan 16;35(2):418-26. PMID:8555211[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN. Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. PMID:26221036 doi:10.1074/jbc.M115.648824
- ↑ Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. PMID:9305882
- ↑ Connolly PJ, Stern AS, Hoch JC. Solution structure of LSIII, a long neurotoxin from the venom of Laticauda semifasciata. Biochemistry. 1996 Jan 16;35(2):418-26. PMID:8555211 doi:http://dx.doi.org/10.1021/bi9520287
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