7w9t

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Current revision (11:46, 30 October 2024) (edit) (undo)
 
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==Cryo-EM structure of human Nav1.7(E406K) in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (S6IV alpha helix conformer)==
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<StructureSection load='7w9t' size='340' side='right'caption='[[7w9t]]' scene=''>
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<StructureSection load='7w9t' size='340' side='right'caption='[[7w9t]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7w9t]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W9T FirstGlance]. <br>
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</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=7w9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w9t OCA], [https://pdbe.org/7w9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w9t RCSB], [https://www.ebi.ac.uk/pdbsum/7w9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w9t ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SL:[(3~{a}~{S},4~{R},10~{a}~{S})-2,6-bis(azanyl)-10,10-bis(oxidanyl)-3~{a},4,8,9-tetrahydro-3~{H}-pyrrolo[1,2-c]purin-4-yl]methyl+carbamate'>9SL</scene>, <scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=LPE:1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>LPE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7w9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w9t OCA], [https://pdbe.org/7w9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w9t RCSB], [https://www.ebi.ac.uk/pdbsum/7w9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w9t ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] Channelopathy-associated congenital insensitivity to pain;Dravet syndrome;Primary erythromelalgia;Sodium channelopathy-related small fiber neuropathy;Generalized epilepsy with febrile seizures-plus;Hereditary sensory and autonomic neuropathy type 2;Paroxysmal extreme pain disorder;Erythromelalgia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] 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 (PubMed:7720699, PubMed:17167479, PubMed:25240195, PubMed:26680203, PubMed:15385606, PubMed:16988069, PubMed:17145499, PubMed:19369487, PubMed:24311784). It is a tetrodotoxin-sensitive Na(+) channel isoform (PubMed:7720699). Plays a role in pain mechanisms, especially in the development of inflammatory pain (PubMed:17167479, PubMed:17145499, PubMed:19369487, PubMed:24311784).<ref>PMID:15178348</ref> <ref>PMID:15385606</ref> <ref>PMID:16988069</ref> <ref>PMID:17145499</ref> <ref>PMID:17167479</ref> <ref>PMID:19369487</ref> <ref>PMID:24311784</ref> <ref>PMID:25240195</ref> <ref>PMID:26680203</ref> <ref>PMID:7720699</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Na(v)1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-A resolution cryo-EM structure of wild-type (WT) Na(v)1.7 complexed with the beta1 and beta2 subunits that reveals several previously indiscernible cytosolic segments. Reprocessing of the cryo-EM data for our reported structures of Na(v)1.7(E406K) bound to various toxins identifies two distinct conformations of S6(IV), one composed of alpha helical turns only and the other containing a pi helical turn in the middle. The structure of ligand-free Na(v)1.7(E406K), determined at 3.5-A resolution, is identical to the WT channel, confirming that binding of Huwentoxin IV or Protoxin II to VSD(II) allosterically induces the alpha --&gt; pi transition of S6(IV). The local secondary structural shift leads to contraction of the intracellular gate, closure of the fenestration on the interface of repeats I and IV, and rearrangement of the binding site for the fast inactivation motif.
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High-resolution structures of human Na(v)1.7 reveal gating modulation through alpha-pi helical transition of S6(IV).,Huang G, Liu D, Wang W, Wu Q, Chen J, Pan X, Shen H, Yan N Cell Rep. 2022 Apr 26;39(4):110735. doi: 10.1016/j.celrep.2022.110735. PMID:35476982<ref>PMID:35476982</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7w9t" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Ion channels 3D structures|Ion channels 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Huang G]]
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[[Category: Liu D]]
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[[Category: Wei P]]
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[[Category: Yan N]]

Current revision

Cryo-EM structure of human Nav1.7(E406K) in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (S6IV alpha helix conformer)

PDB ID 7w9t

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