3ZKR

X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) in complex with bromoform

Summary for 3ZKR

• Entry DOI: 10.2210/pdb3zkr/pdb
• Descriptor: CYS-LOOP LIGAND-GATED ION CHANNEL, TRIBROMOMETHANE (2 entities in total)
• Functional Keywords: transport protein, cys-loop receptor, gaba-a receptor, general anesthetics
• Biological source: ERWINIA CHRYSANTHEMI
• Cellular location: Cell inner membrane; Multi-pass membrane protein (Probable): P0C7B7
• Total number of polymer chains: 10
• Total formula weight: 359393.75

Authors

Spurny, R.,Billen, B.,Howard, R.J.,Brams, M.,Debaveye, S.,Price, K.L.,Weston, D.A.,Strelkov, S.V.,Tytgat, J.,Bertrand, S.,Bertrand, D.,Lummis, S.C.R.,Ulens, C. (deposition date: 2013-01-24, release date: 2013-02-06, Last modification date: 2024-05-08)

Primary citation

Spurny, R.,Billen, B.,Howard, R.J.,Brams, M.,Debaveye, S.,Price, K.L.,Weston, D.A.,Strelkov, S.V.,Tytgat, J.,Bertrand, S.,Bertrand, D.,Lummis, S.C.R.,Ulens, C.
Multisite Binding of a General Anesthetic to the Prokaryotic Pentameric Erwinia Chrysanthemi Ligand-Gated Ion Channel (Elic).
J.Biol.Chem., 288:8355-, 2013

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABA(A/C) receptors, and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anesthetics. Here, we report the x-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore and equates with a noncompetitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7-β10 strands. Together, these results extend our understanding of pLGIC modulation and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multisite model of allosteric modulation in this family of ion channels.

PubMed: 23364792
DOI: 10.1074/JBC.M112.424507

Experimental method

X-RAY DIFFRACTION (3.649 Å)