4cbc

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==Open-form NavMS Sodium Channel Pore (with C-terminal Domain) after thallium soak==
==Open-form NavMS Sodium Channel Pore (with C-terminal Domain) after thallium soak==
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<StructureSection load='4cbc' size='340' side='right' caption='[[4cbc]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
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<StructureSection load='4cbc' size='340' side='right'caption='[[4cbc]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4cbc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CBC FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4cbc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Magnetococcus_marinus_MC-1 Magnetococcus marinus MC-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CBC FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2CV:HEGA-10'>2CV</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.664&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cal|4cal]], [[4cbd|4cbd]]</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=2CV:HEGA-10'>2CV</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cbc RCSB], [http://www.ebi.ac.uk/pdbsum/4cbc PDBsum]</span></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=4cbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbc OCA], [https://pdbe.org/4cbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cbc RCSB], [https://www.ebi.ac.uk/pdbsum/4cbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbc ProSAT]</span></td></tr>
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<table>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/A0L5S6_MAGMM A0L5S6_MAGMM]
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 A resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil.
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Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs channel can be a valuable tool for screening and rational design of human drugs.
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Role of the C-terminal domain in the structure and function of tetrameric sodium channels.,Bagneris C, Decaen PG, Hall BA, Naylor CE, Clapham DE, Kay CW, Wallace BA Nat Commun. 2013 Sep 20;4:2465. doi: 10.1038/ncomms3465. PMID:24051986<ref>PMID:24051986</ref>
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Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.,Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA Proc Natl Acad Sci U S A. 2014 May 21. pii: 201406855. PMID:24850863<ref>PMID:24850863</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 4cbc" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bagneris, C.]]
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[[Category: Large Structures]]
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[[Category: Naylor, C E.]]
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[[Category: Magnetococcus marinus MC-1]]
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[[Category: Wallace, B A.]]
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[[Category: Bagneris C]]
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[[Category: Membrane protein]]
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[[Category: Naylor CE]]
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[[Category: Selectivity filter]]
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[[Category: Wallace BA]]
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[[Category: Sodium channel]]
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[[Category: Transport protein]]
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Current revision

Open-form NavMS Sodium Channel Pore (with C-terminal Domain) after thallium soak

PDB ID 4cbc

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