View source for 7k18


==Cardiac Sodium channel with toxin bound==
<StructureSection load='7k18' size='340' side='right'caption='[[7k18]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7k18]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria], [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus] 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=7K18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K18 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</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=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=7k18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k18 OCA], [https://pdbe.org/7k18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k18 RCSB], [https://www.ebi.ac.uk/pdbsum/7k18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k18 ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== Publication Abstract from PubMed ==
Voltage-gated sodium (Na(V)) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The alpha-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac Na(V)1.5 channels with IC(50) = 11.4 nM. Here we reveal the structure of LqhIII bound to Na(V)1.5 at 3.3 A resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na(+) permeation, revealing why LqhIII slows inactivation of Na(V) channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of Na(V) channels.

Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin.,Jiang D, Tonggu L, Gamal El-Din TM, Banh R, Pomes R, Zheng N, Catterall WA Nat Commun. 2021 Jan 4;12(1):128. doi: 10.1038/s41467-020-20078-3. PMID:33397917<ref>PMID:33397917</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7k18" 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__
</StructureSection>
[[Category: Aequorea victoria]]
[[Category: Large Structures]]
[[Category: Leiurus hebraeus]]
[[Category: Rattus norvegicus]]
[[Category: Catterall WA]]
[[Category: Jiang D]]