4ms2: Difference between revisions
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==Structural basis of Ca2+ selectivity of a voltage-gated calcium channel== | |||
<StructureSection load='4ms2' size='340' side='right' caption='[[4ms2]], [[Resolution|resolution]] 2.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ms2]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MS2 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> | |||
<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=4ms2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ms2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ms2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ms2 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
[[Category: Catterall, W A | <references/> | ||
[[Category: El-Din, T M.Gamal | __TOC__ | ||
</StructureSection> | |||
[[Category: Catterall, W A]] | |||
[[Category: El-Din, T M.Gamal]] | |||
[[Category: Heard, T M]] | [[Category: Heard, T M]] | ||
[[Category: Martinez, G Q | [[Category: Martinez, G Q]] | ||
[[Category: Payandeh, J | [[Category: Payandeh, J]] | ||
[[Category: Scheuer, T | [[Category: Scheuer, T]] | ||
[[Category: Tang, L | [[Category: Tang, L]] | ||
[[Category: Zheng, N]] | [[Category: Zheng, N]] | ||
[[Category: Calcium selective]] | [[Category: Calcium selective]] | ||
