View source for 8vqc


==Structure of the voltage-gated sodium channel NavPas from American Cockroach Periplaneta Americana in complex with scorpion alpha-toxin LqhaIT==
<StructureSection load='8vqc' size='340' side='right'caption='[[8vqc]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vqc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus] and [https://en.wikipedia.org/wiki/Periplaneta_americana Periplaneta americana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VQC 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]] 3.9&#8491;</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=8vqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vqc OCA], [https://pdbe.org/8vqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vqc RCSB], [https://www.ebi.ac.uk/pdbsum/8vqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vqc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SCNA1_PERAM SCNA1_PERAM] Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132]<ref>PMID:28183995</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. The deathstalker scorpion alpha-toxin LqhalphaIT exerts a strong action potential prolonging effect on Nav channels. To elucidate the mechanism of action of LqhalphaIT, we determined a 3.9 A cryoelectron microscopy (cryo-EM) structure of LqhalphaIT in complex with the Nav channel from Periplaneta americana (NavPas). We found that LqhalphaIT binds to voltage sensor domain 4 and traps it in an "S4 down" conformation. The functionally essential C-terminal epitope of LqhalphaIT forms an extensive interface with the glycan scaffold linked to Asn330 of NavPas that augments a small protein-protein interface between NavPas and LqhalphaIT. A combination of molecular dynamics simulations, structural comparisons, and prior mutagenesis experiments demonstrates the functional importance of this toxin-glycan interaction. These findings establish a structural basis for the specificity achieved by scorpion alpha-toxins and reveal the conserved glycan as an essential component of the toxin-binding epitope.

Scorpion alpha-toxin LqhalphaIT specifically interacts with a glycan at the pore domain of voltage-gated sodium channels.,Phulera S, Dickson CJ, Schwalen CJ, Khoshouei M, Cassell SJ, Sun Y, Condos T, Whicher J, Weihofen WA Structure. 2024 Aug 17:S0969-2126(24)00284-3. doi: 10.1016/j.str.2024.07.021. PMID:39181123<ref>PMID:39181123</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vqc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leiurus hebraeus]]
[[Category: Periplaneta americana]]
[[Category: Khoshouei M]]
[[Category: Phulera S]]
[[Category: Weihofen WA]]
[[Category: Whicher J]]