6uz3: Difference between revisions

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==Cardiac sodium channel==
==Cardiac sodium channel==
<StructureSection load='6uz3' size='340' side='right'caption='[[6uz3]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
<SX load='6uz3' size='340' side='right' viewer='molstar' caption='[[6uz3]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6uz3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UZ3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6uz3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZ3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6OU:[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl]+(~{Z})-octadec-9-enoate'>6OU</scene>, <scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</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=6uz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uz3 OCA], [http://pdbe.org/6uz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uz3 RCSB], [http://www.ebi.ac.uk/pdbsum/6uz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uz3 ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OU:[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl]+(~{Z})-octadec-9-enoate'>6OU</scene>, <scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6uz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uz3 OCA], [https://pdbe.org/6uz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uz3 RCSB], [https://www.ebi.ac.uk/pdbsum/6uz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uz3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SCN5A_RAT SCN5A_RAT]] This protein 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 Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.[UniProtKB:Q14524][UniProtKB:Q9JJV9]  
[https://www.uniprot.org/uniprot/SCN5A_RAT SCN5A_RAT] This protein 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 Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.[UniProtKB:Q14524][UniProtKB:Q9JJV9][https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Voltage-gated sodium channel Nav1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of NaV1.5 at 3.2-3.5 A resolution. NaV1.5 is distinguished from other sodium channels by a unique glycosyl moiety and loss of disulfide-bonding capability at the NaVbeta subunit-interaction sites. The antiarrhythmic drug flecainide specifically targets the central cavity of the pore. The voltage sensors are partially activated, and the fast-inactivation gate is partially closed. Activation of the voltage sensor of Domain III allows binding of the isoleucine-phenylalanine-methionine (IFM) motif to the inactivation-gate receptor. Asp and Ala, in the selectivity motif DEKA, line the walls of the ion-selectivity filter, whereas Glu and Lys are in positions to accept and release Na(+) ions via a charge-delocalization network. Arrhythmia mutation sites undergo large translocations during gating, providing a potential mechanism for pathogenic effects. Our results provide detailed insights into Nav1.5 structure, pharmacology, activation, inactivation, ion selectivity, and arrhythmias.
 
Structure of the Cardiac Sodium Channel.,Jiang D, Shi H, Tonggu L, Gamal El-Din TM, Lenaeus MJ, Zhao Y, Yoshioka C, Zheng N, Catterall WA Cell. 2019 Dec 13. pii: S0092-8674(19)31326-1. doi: 10.1016/j.cell.2019.11.041. PMID:31866066<ref>PMID:31866066</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uz3" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]]
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Aequorea victoria]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Catterall, W A]]
[[Category: Rattus norvegicus]]
[[Category: Jiang, D]]
[[Category: Catterall WA]]
[[Category: Lenaeus, M J]]
[[Category: Jiang D]]
[[Category: Shi, H]]
[[Category: Lenaeus MJ]]
[[Category: Tonggu, L]]
[[Category: Shi H]]
[[Category: Zheng, N]]
[[Category: Tonggu L]]
[[Category: Cardiac sodium channel]]
[[Category: Zheng N]]
[[Category: Ion channel]]
[[Category: Metal transport]]

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