View source for 9dbl


==Full-length apo human voltage-gated sodium channel 1.8 (NaV1.8), class I==
<StructureSection load='9dbl' size='340' side='right'caption='[[9dbl]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dbl]] is a 1 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=9DBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DBL 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]] 3.24&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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></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=9dbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dbl OCA], [https://pdbe.org/9dbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dbl RCSB], [https://www.ebi.ac.uk/pdbsum/9dbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dbl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SCNAA_HUMAN SCNAA_HUMAN] Brugada syndrome;Primary erythromelalgia;Hereditary sodium channelopathy-related small fibers neuropathy;Paroxysmal extreme pain disorder;Romano-Ward syndrome;Congenital insensitivity to pain-anosmia-neuropathic arthropathy. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SCNAA_HUMAN SCNAA_HUMAN] Tetrodotoxin-resistant channel that 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 sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.<ref>PMID:23115331</ref> <ref>PMID:9839820</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Voltage-gated sodium channels (Na(V)s) selectively permit diffusion of sodium ions across the cell membrane and, in excitable cells, are responsible for propagating action potentials. One of the nine human Na(V) isoforms, Na(V)1.8, is a promising target for analgesics, and selective inhibitors are of interest as therapeutics. One such inhibitor, the gating-modifier peptide Protoxin-I derived from tarantula venom, blocks channel opening by shifting the activation voltage threshold to more depolarized potentials, but the structural basis for this inhibition has not previously been determined. Using monolayer graphene grids, we report the cryogenic electron microscopy structures of full-length human apo-Na(V)1.8 and the Protoxin-I-bound complex at 3.1 A and 2.8 A resolution, respectively. The apo structure shows an unexpected movement of the Domain I S4-S5 helix, and VSD(I) was unresolvable. We find that Protoxin-I binds to and displaces the VSD(II) S3-S4 linker, hindering translocation of the S4(II) helix during activation.

Structural basis of inhibition of human Na(V)1.8 by the tarantula venom peptide Protoxin-I.,Neumann B, McCarthy S, Gonen S Nat Commun. 2025 Feb 7;16(1):1459. doi: 10.1038/s41467-024-55764-z. PMID:39920100<ref>PMID:39920100</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dbl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gonen S]]
[[Category: McCarthy S]]
[[Category: Neumann B]]