6mwd: Difference between revisions
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==NavAb Voltage-gated Sodium Channel, residues 1-239 with mutation T206S== | |||
<StructureSection load='6mwd' size='340' side='right' caption='[[6mwd]], [[Resolution|resolution]] 2.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mwd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MWD FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6mwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mwd OCA], [http://pdbe.org/6mwd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mwd RCSB], [http://www.ebi.ac.uk/pdbsum/6mwd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mwd ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Homotetrameric bacterial voltage-gated sodium channels share major biophysical features with their more complex eukaryotic counterparts, including a slow-inactivation mechanism that reduces ion-conductance activity during prolonged depolarization through conformational changes in the pore. The bacterial sodium channel NaVAb activates at very negative membrane potentials and inactivates through a multiphase slow-inactivation mechanism. Early voltage-dependent inactivation during one depolarization is followed by late use-dependent inactivation during repetitive depolarization. Mutations that change the molecular volume of Thr206 in the pore-lining S6 segment can enhance or strongly block early voltage-dependent inactivation, suggesting that this residue serves as a molecular hub controlling the coupling of activation to inactivation. In contrast, truncation of the C-terminal tail enhances the early phase of inactivation yet completely blocks late use-dependent inactivation. Determination of the structure of a C-terminal tail truncation mutant and molecular modeling of conformational changes at Thr206 and the S6 activation gate led to a two-step model of these gating processes. First, bending of the S6 segment, local protein interactions dependent on the size of Thr206, and exchange of hydrogen-bonding partners at the level of Thr206 trigger pore opening followed by the early phase of voltage-dependent inactivation. Thereafter, conformational changes in the C-terminal tail lead to late use-dependent inactivation. These results have important implications for the sequence of conformational changes that lead to multiphase inactivation of NaVAb and other sodium channels. | |||
Molecular dissection of multiphase inactivation of the bacterial sodium channel NaVAb.,Gamal El-Din TM, Lenaeus MJ, Ramanadane K, Zheng N, Catterall WA J Gen Physiol. 2018 Dec 3. pii: jgp.201711884. doi: 10.1085/jgp.201711884. PMID:30510035<ref>PMID:30510035</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: Catterall, W | <div class="pdbe-citations 6mwd" style="background-color:#fffaf0;"></div> | ||
[[Category: Lenaeus, M | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Catterall, W A]] | |||
[[Category: Lenaeus, M J]] | |||
[[Category: Ion channel voltage-gated sodium channel]] | |||
[[Category: Membrane protein]] | |||
[[Category: Metal transport]] | |||
