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| | ==Structural Basis for Ca2+ Selectivity of a Voltage-gated Calcium Channel== | | ==Structural Basis for Ca2+ Selectivity of a Voltage-gated Calcium Channel== |
| - | <StructureSection load='4mvo' size='340' side='right' caption='[[4mvo]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='4mvo' size='340' side='right'caption='[[4mvo]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mvo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Arcb4 Arcb4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MVO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mvo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aliarcobacter_butzleri_RM4018 Aliarcobacter butzleri RM4018]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MVO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.296Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ms2|4ms2]], [[4mtf|4mtf]], [[4mtg|4mtg]], [[4mto|4mto]], [[4mvm|4mvm]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Abu_1752 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=367737 ARCB4])</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=4mvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mvo OCA], [https://pdbe.org/4mvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mvo RCSB], [https://www.ebi.ac.uk/pdbsum/4mvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mvo ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mvo OCA], [http://pdbe.org/4mvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mvo RCSB], [http://www.ebi.ac.uk/pdbsum/4mvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mvo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A8EVM5_ALIB4 A8EVM5_ALIB4] |
| - | Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca2+ into cells despite a 70-fold higher extracellular concentration of Na+. How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca2+ with two high-affinity Ca2+-binding sites followed by a third lower-affinity site that would coordinate Ca2+ as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca2+ selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd2+ and Mn2+, with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca2+ ions bound in the selectivity filter and supports a 'knock-off' mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels.
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| - | Structural basis for Ca selectivity of a voltage-gated calcium channel.,Tang L, Gamal El-Din TM, Payandeh J, Martinez GQ, Heard TM, Scheuer T, Zheng N, Catterall WA Nature. 2013 Nov 24. doi: 10.1038/nature12775. PMID:24270805<ref>PMID:24270805</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4mvo" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arcb4]] | + | [[Category: Aliarcobacter butzleri RM4018]] |
| - | [[Category: Catterall, W A]] | + | [[Category: Large Structures]] |
| - | [[Category: El-Din, T M.Gamal]] | + | [[Category: Catterall WA]] |
| - | [[Category: Heard, T M]] | + | [[Category: Gamal El-Din TM]] |
| - | [[Category: Martinez, G Q]] | + | [[Category: Heard TM]] |
| - | [[Category: Payandeh, J]] | + | [[Category: Martinez GQ]] |
| - | [[Category: Scheuer, T]] | + | [[Category: Payandeh J]] |
| - | [[Category: Tang, L]] | + | [[Category: Scheuer T]] |
| - | [[Category: Zheng, N]] | + | [[Category: Tang L]] |
| - | [[Category: Calcium selective]]
| + | [[Category: Zheng N]] |
| - | [[Category: Membrane]]
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| - | [[Category: Metal transport]]
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| - | [[Category: Tetrameric]]
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| - | [[Category: Transport protein]]
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| - | [[Category: Voltage-gated calcium channel]]
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| - | [[Category: Voltage-gated ion channel]]
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