3RQW
Crystal structure of acetylcholine bound to a prokaryotic pentameric ligand-gated ion channel, ELIC
Summary for 3RQW
Entry DOI | 10.2210/pdb3rqw/pdb |
Related | 3RQU |
Descriptor | ELIC Pentameric Ligand Gated Ion Channel from Erwinia Chrysanthemi, ACETYLCHOLINE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total) |
Functional Keywords | ion channel, membrane, transport protein |
Biological source | Dickeya dadantii (Erwinia chrysanthemi) |
Total number of polymer chains | 10 |
Total formula weight | 374495.74 |
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 citation | Pan, 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: 22395605DOI: 10.1038/ncomms1703 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.913 Å) |
Structure validation
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