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X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation


Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction1,2,3, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 Å resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue4 (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons5. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 Å constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity6,7,8,9. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation10, shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular β-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 α-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.

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Figure 1: GLIC structure.
Figure 2: GLIC and ELIC pores.
Figure 3: Open GLIC and closed ELIC structure comparison.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Coordinates of GLIC have been deposited in the Protein Data Bank under accession number 3eam.


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We thank P. Koehl for his program Aquasol and help with electrostatic calculations; P. Delepelaire and S. Edelstein for discussions; the staff of ESRF (Grenoble) ID14 and ID23 beamlines for data collection; facilities of the Pasteur Institute (A. Haouz for crystallogenesis, P. England for ultracentrifugation experiments, J. d’Alayer for mass spectroscopy controls and J. Bellalou for help in protein expression); and B. De Foresta (CEA, Orsay) for a gift of the two brominated DDM analogues. The latter diffraction data sets were collected at SLS and PSI (Villingen, Switzerland). We thank M. Fuchs for assistance during data collection; and the IDRIS supercomputer centre and its support staff for allocating CPU time at very short notice (project 082292). This work was supported by the Région Ile-de-France (N.B.), the Association Française contre les Myopathies, the Collège de France (C.L.P.), the Commission of the European Communities (Neurocypres project; H.N.) and the Network of European Neuroscience Institutes (ENI-NET).

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Correspondence to Marc Delarue or Pierre-Jean Corringer.

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Supplementary Information

This file contains Supplementary Methods, Supplementary Tables S1- S2, Supplementary Figures S1-S8 and Supplementary References (PDF 2411 kb)

Supplementary Movie

The Supplementary Movie file illustrates the conformational dynamics of the system. The GLIC structure remains in an open conformation during the whole production run (20 ns), exhibiting thermal fluctuations around an average structure in its transmembrane part. The extracellular part is more mobile. (ZIP 8194 kb)

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Bocquet, N., Nury, H., Baaden, M. et al. X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 111–114 (2009).

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