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3RQW

Crystal structure of acetylcholine bound to a prokaryotic pentameric ligand-gated ion channel, ELIC

Summary for 3RQW
Entry DOI10.2210/pdb3rqw/pdb
Related3RQU
DescriptorELIC Pentameric Ligand Gated Ion Channel from Erwinia Chrysanthemi, ACETYLCHOLINE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
Functional Keywordsion channel, membrane, transport protein
Biological sourceDickeya dadantii (Erwinia chrysanthemi)
Total number of polymer chains10
Total formula weight374495.74
Authors
Pan, J.J.,Chen, Q.,Yoshida, K.,Cohen, A.,Kong, X.P.,Xu, Y.,Tang, P. (deposition date: 2011-04-28, release date: 2012-03-07, Last modification date: 2023-09-13)
Primary citationPan, J.,Chen, Q.,Willenbring, D.,Yoshida, K.,Tillman, T.,Kashlan, O.B.,Cohen, A.,Kong, X.P.,Xu, Y.,Tang, P.
Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine.
Nat Commun, 3:714-714, 2012
Cited by
PubMed Abstract: 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-Å 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-π 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.
PubMed: 22395605
DOI: 10.1038/ncomms1703
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.913 Å)
Structure validation

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