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| | ==Crystal structure of the NavAb voltage-gated sodium channel (Ile217Cys, 2.8 A)== | | ==Crystal structure of the NavAb voltage-gated sodium channel (Ile217Cys, 2.8 A)== |
| - | <StructureSection load='3rvz' size='340' side='right' caption='[[3rvz]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3rvz' size='340' side='right'caption='[[3rvz]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rvz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arcobacter_butzleri Arcobacter butzleri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RVZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rvz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aliarcobacter_butzleri_RM4018 Aliarcobacter butzleri RM4018]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RVZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rvy|3rvy]], [[3rw0|3rw0]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Abu_1752 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28197 Arcobacter butzleri])</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=3rvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rvz OCA], [https://pdbe.org/3rvz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rvz RCSB], [https://www.ebi.ac.uk/pdbsum/3rvz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rvz ProSAT]</span></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=3rvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rvz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rvz RCSB], [http://www.ebi.ac.uk/pdbsum/3rvz PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A8EVM5_ALIB4 A8EVM5_ALIB4] |
| - | Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 A resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, approximately 4.6 A wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na(+) selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.
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| - | The crystal structure of a voltage-gated sodium channel.,Payandeh J, Scheuer T, Zheng N, Catterall WA Nature. 2011 Jul 10;475(7356):353-8. doi: 10.1038/nature10238. PMID:21743477<ref>PMID:21743477</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| - | == References == | + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arcobacter butzleri]] | + | [[Category: Aliarcobacter butzleri RM4018]] |
| - | [[Category: Catterall, W A]] | + | [[Category: Large Structures]] |
| - | [[Category: Payandeh, J]] | + | [[Category: Catterall WA]] |
| - | [[Category: Scheuer, T]] | + | [[Category: Payandeh J]] |
| - | [[Category: Zheng, N]] | + | [[Category: Scheuer T]] |
| - | [[Category: Membrane]]
| + | [[Category: Zheng N]] |
| - | [[Category: Metal transport]]
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| - | [[Category: Tetrameric ion channel]]
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| - | [[Category: Voltage-gated sodium-selective ion channel]]
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