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8eoi
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Structure of a human EMC:human Cav1.2 channel complex in GDN detergent== |
| + | <StructureSection load='8eoi' size='340' side='right'caption='[[8eoi]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8eoi]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EOI 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]] 3.4Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</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=8eoi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eoi OCA], [https://pdbe.org/8eoi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eoi RCSB], [https://www.ebi.ac.uk/pdbsum/8eoi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eoi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/EMC1_HUMAN EMC1_HUMAN] Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/EMC1_HUMAN EMC1_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Voltage-gated ion channels (VGICs) comprise multiple structural units whose assembly is required for function(1,2). There is scant structural understanding of how VGIC subunits assemble and whether chaperone proteins are required. High-voltage activated calcium channels (Ca(V)s)(3,4) are paradigmatic multi-subunit VGICs whose function and trafficking is powerfully shaped by interactions between pore-forming Ca(V)1 or Ca(V)2 Ca(V)alpha(1)(3) and auxiliary Ca(V)beta(5), and Ca(V)alpha(2)delta subunits(6,7). Here, we present cryo-EM structures of human brain and cardiac Ca(V)1.2 bound with Ca(V)beta(3) to a chaperone, the endoplasmic reticulum membrane protein complex (EMC)(8,9), and of the assembled Ca(V)1.2/Ca(V)beta(3)/Ca(V)alpha(2)delta-1 channel. These provide a view of an EMC:client complex and define EMC sites, the TM and Cyto docks, whose interaction with the client channel causes partial extraction of a pore subunit and splays open the Ca(V)alpha(2)delta interaction site. The structures identify the Ca(V)alpha(2)delta binding site for gabapentinoid anti-pain and anti-anxiety drugs(6), show that EMC and Ca(V)alpha(2)delta channel interactions are mutually exclusive, and indicate that EMC to Ca(V)alpha(2)delta handoff involves a divalent ion-dependent step and Ca(V)1.2 element ordering. Disruption of the EMC:Ca(V) complex compromises Ca(V) function suggesting that the EMC acts as a channel holdase that facilitates channel assembly. Together, the structures unveil a Ca(V) assembly intermediate and EMC client binding sites, with potentially wide-reading implications for biogenesis of VGICs and other membrane proteins. | ||
| - | + | EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate.,Chen Z, Mondal A, Ali FA, Jang S, Niranjan S, Montano JL, Zaro BW, Minor DL Jr Nature. 2023 May 17. doi: 10.1038/s41586-023-06175-5. PMID:37196677<ref>PMID:37196677</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8eoi" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ion channels 3D structures|Ion channels 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Oryctolagus cuniculus]] | ||
| + | [[Category: Abderemane-Ali F]] | ||
| + | [[Category: Chen Z]] | ||
| + | [[Category: Minor DL]] | ||
| + | [[Category: Mondal A]] | ||
Current revision
Structure of a human EMC:human Cav1.2 channel complex in GDN detergent
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