6mwg: Difference between revisions
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==NavAb Voltage-gated Sodium Channel, residues 1-239, with mutation T206V== | |||
<StructureSection load='6mwg' size='340' side='right' caption='[[6mwg]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mwg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MWG 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></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=6mwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mwg OCA], [http://pdbe.org/6mwg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mwg RCSB], [http://www.ebi.ac.uk/pdbsum/6mwg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mwg 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 6mwg" 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]] | |||
Revision as of 11:34, 19 December 2018
Structural highlights
Publication Abstract from PubMedHomotetrameric 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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