View source for 7miy


==Human N-type voltage-gated calcium channel Cav2.2 at 3.1 Angstrom resolution==
<StructureSection load='7miy' size='340' side='right'caption='[[7miy]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7miy]] is a 3 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=7MIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MIY 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PT5:(1S)-2-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(8E,11E)-ICOSA-5,8,11,14-TETRAENOATE'>PT5</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7miy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7miy OCA], [https://pdbe.org/7miy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7miy RCSB], [https://www.ebi.ac.uk/pdbsum/7miy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7miy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAC1B_HUMAN CAC1B_HUMAN] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The neuronal-type (N-type) voltage-gated calcium (Ca(v)) channels, which are designated Ca(v)2.2, have an important role in the release of neurotransmitters(1-3). Ziconotide is a Ca(v)2.2-specific peptide pore blocker that has been clinically used for treating intractable pain(4-6). Here we present cryo-electron microscopy structures of human Ca(v)2.2 (comprising the core alpha1 and the ancillary alpha2delta-1 and beta3 subunits) in the presence or absence of ziconotide. Ziconotide is thoroughly coordinated by helices P1 and P2, which support the selectivity filter, and the extracellular loops (ECLs) in repeats II, III and IV of alpha1. To accommodate ziconotide, the ECL of repeat III and alpha2delta-1 have to tilt upward concertedly. Three of the voltage-sensing domains (VSDs) are in a depolarized state, whereas the VSD of repeat II exhibits a down conformation that is stabilized by Ca(v)2-unique intracellular segments and a phosphatidylinositol 4,5-bisphosphate molecule. Our studies reveal the molecular basis for Ca(v)2.2-specific pore blocking by ziconotide and establish the framework for investigating electromechanical coupling in Ca(v) channels.

Structure of human Ca(v)2.2 channel blocked by the painkiller ziconotide.,Gao S, Yao X, Yan N Nature. 2021 Aug;596(7870):143-147. doi: 10.1038/s41586-021-03699-6. Epub 2021 , Jul 7. PMID:34234349<ref>PMID:34234349</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 7miy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gao S]]
[[Category: Yan N]]
[[Category: Yao X]]