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]. 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:(1~{S},2~{S},4~{S},5~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-16-[4-methoxy-3-(methoxymethyl)butoxy]-5,7,9,13-tetramethyl-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2-oxane]'>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, the assembly of which is required for function(1,2). Structural understanding of how VGIC subunits assemble and whether chaperone proteins are required is lacking. High-voltage-activated calcium channels (Ca(V)s)(3,4) are paradigmatic multisubunit VGICs whose function and trafficking are powerfully shaped by interactions between pore-forming Ca(V)1 or Ca(V)2 Ca(V)alpha(1) (ref. (3)), and the auxiliary Ca(V)beta(5) and Ca(V)alpha(2)delta subunits(6,7). Here we present cryo-electron microscopy 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 structures provide a view of an EMC-client complex and define EMC sites-the transmembrane (TM) and cytoplasmic (Cyto) docks; interaction between these sites and 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 interactions with the channel are mutually exclusive, and indicate that EMC-to-Ca(V)alpha(2)delta hand-off 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 functions as a channel holdase that facilitates channel assembly. Together, the structures reveal a Ca(V) assembly intermediate and EMC client-binding sites that could have wide-ranging implications for the biogenesis of VGICs and other membrane proteins. | ||
| - | + | EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate.,Chen Z, Mondal A, Abderemane-Ali F, Jang S, Niranjan S, Montano JL, Zaro BW, Minor DL Jr Nature. 2023 Jul;619(7969):410-419. doi: 10.1038/s41586-023-06175-5. Epub 2023 , May 17. 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: 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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