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[[ | ==Crystal structure of acetylcholine bound to a prokaryotic pentameric ligand-gated ion channel, ELIC== | ||
<StructureSection load='3rqw' size='340' side='right' caption='[[3rqw]], [[Resolution|resolution]] 2.91Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rqw]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Dickeya_dadantii Dickeya dadantii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RQW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RQW FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACH:ACETYLCHOLINE'>ACH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rqu|3rqu]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dda3937_00520 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=204038 Dickeya dadantii])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rqw RCSB], [http://www.ebi.ac.uk/pdbsum/3rqw PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ELIC, the pentameric ligand-gated ion channel from Erwinia chrysanthemi, is a prototype for Cys-loop receptors. Here we show that acetylcholine is a competitive antagonist for ELIC. We determine the acetylcholine-ELIC cocrystal structure to a 2.9-A resolution and find that acetylcholine binding to an aromatic cage at the subunit interface induces a significant contraction of loop C and other structural rearrangements in the extracellular domain. The side chain of the pore-lining residue F247 reorients and the pore size consequently enlarges, but the channel remains closed. We attribute the inability of acetylcholine to activate ELIC primarily to weak cation-pi and electrostatic interactions in the pocket, because an acetylcholine derivative with a simple quaternary-to-tertiary ammonium substitution activates the channel. This study presents a compelling case for understanding the structural underpinning of the functional relationship between agonism and competitive antagonism in the Cys-loop receptors, providing a new framework for developing novel therapeutic drugs. | |||
Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine.,Pan J, Chen Q, Willenbring D, Yoshida K, Tillman T, Kashlan OB, Cohen A, Kong XP, Xu Y, Tang P Nat Commun. 2012 Mar 6;3:714. doi: 10.1038/ncomms1703. PMID:22395605<ref>PMID:22395605</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Dickeya dadantii]] | [[Category: Dickeya dadantii]] | ||
[[Category: Chen, Q.]] | [[Category: Chen, Q.]] | ||
Revision as of 07:52, 5 June 2014
Crystal structure of acetylcholine bound to a prokaryotic pentameric ligand-gated ion channel, ELICCrystal structure of acetylcholine bound to a prokaryotic pentameric ligand-gated ion channel, ELIC
Structural highlights
Publication Abstract from PubMedELIC, the pentameric ligand-gated ion channel from Erwinia chrysanthemi, is a prototype for Cys-loop receptors. Here we show that acetylcholine is a competitive antagonist for ELIC. We determine the acetylcholine-ELIC cocrystal structure to a 2.9-A resolution and find that acetylcholine binding to an aromatic cage at the subunit interface induces a significant contraction of loop C and other structural rearrangements in the extracellular domain. The side chain of the pore-lining residue F247 reorients and the pore size consequently enlarges, but the channel remains closed. We attribute the inability of acetylcholine to activate ELIC primarily to weak cation-pi and electrostatic interactions in the pocket, because an acetylcholine derivative with a simple quaternary-to-tertiary ammonium substitution activates the channel. This study presents a compelling case for understanding the structural underpinning of the functional relationship between agonism and competitive antagonism in the Cys-loop receptors, providing a new framework for developing novel therapeutic drugs. Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine.,Pan J, Chen Q, Willenbring D, Yoshida K, Tillman T, Kashlan OB, Cohen A, Kong XP, Xu Y, Tang P Nat Commun. 2012 Mar 6;3:714. doi: 10.1038/ncomms1703. PMID:22395605[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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