8t6l
From Proteopedia
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<table><tr><td colspan='2'>[[8t6l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8T6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8T6L FirstGlance]. <br> | <table><tr><td colspan='2'>[[8t6l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8T6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8T6L FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=LBN: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=LBN:[(2~{R})-3-hexadecanoyloxy-2-[(~{Z})-octadec-9-enoyl]oxy-propyl]+2-(trimethylazaniumyl)ethyl+phosphate'>LBN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=YIJ:(1R)-1-[(5aR,7aR,9R,11aS,11bS,12R,13aR)-9,12-dihydroxy-2,11a-dimethyl-1,2,3,4,7a,8,9,10,11,11a,12,13-dodecahydro-7H-9,11b-epoxy-13a,5a-prop[1]enophenanthro[2,1-f][1,4]oxazepin-14-yl]ethyl+benzoate'>YIJ</scene></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=8t6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8t6l OCA], [https://pdbe.org/8t6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8t6l RCSB], [https://www.ebi.ac.uk/pdbsum/8t6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8t6l 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=8t6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8t6l OCA], [https://pdbe.org/8t6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8t6l RCSB], [https://www.ebi.ac.uk/pdbsum/8t6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8t6l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/SCN5A_RAT SCN5A_RAT] This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.[UniProtKB:Q14524][UniProtKB:Q9JJV9][https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. | [https://www.uniprot.org/uniprot/SCN5A_RAT SCN5A_RAT] This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.[UniProtKB:Q14524][UniProtKB:Q9JJV9][https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic electron microscopy, we identify two homologous, but nonidentical receptor sites that simultaneously bind two molecules of toxin, one at the interface between Domains I and IV, and the other at the interface between Domains III and IV of the cardiac sodium channel. Together, these two bound toxin molecules stabilize alpha/pi helical conformation in the S6 segments that gate the pore, and one of the bound BTX-B molecules interacts with the crucial Lys1421 residue that is essential for sodium conductance and selectivity via an apparent water-bridged hydrogen bond. Overall, our structure provides insight into batrachotoxin's potency, efficacy, and multifaceted functional effects on voltage-gated sodium channels via a dual receptor site mechanism. | ||
| + | |||
| + | Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin.,Tonggu L, Wisedchaisri G, Gamal El-Din TM, Lenaeus MJ, Logan MM, Toma T, Du Bois J, Zheng N, Catterall WA Nat Commun. 2024 Mar 14;15(1):2306. doi: 10.1038/s41467-024-45958-w. PMID:38485923<ref>PMID:38485923</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8t6l" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Cryo-EM structure of rat cardiac sodium channel NaV1.5 with batrachotoxin analog BTX-B
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