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PDBsum entry 3eam
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Membrane protein, transport protein
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PDB id
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3eam
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of a pentameric ligand-Gated ion channel in an apparently open conformation.
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Authors
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N.Bocquet,
H.Nury,
M.Baaden,
C.Le poupon,
J.P.Changeux,
M.Delarue,
P.J.Corringer.
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Ref.
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Nature, 2009,
457,
111-114.
[DOI no: ]
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PubMed id
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Abstract
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Pentameric ligand-gated ion channels from the Cys-loop family mediate fast
chemo-electrical transduction, but the mechanisms of ion permeation and gating
of these membrane proteins remain elusive. Here we present the X-ray structure
at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric
ligand-gated ion channel homologue (GLIC) at pH 4.6 in an apparently open
conformation. This cationic channel is known to be permanently activated by
protons. 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
A constriction matches with rings of hydrophilic residues that are likely to
contribute to the ionic selectivity. Structural comparison with ELIC, a
bacterial homologue from Erwinia chrysanthemi solved in a presumed closed
conformation, 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 beta-sandwich domain as a rigid body, interface
rearrangements, and a reorganization of the transmembrane domain, involving a
tilt of the M2 and M3 alpha-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.
Figure 1: GLIC structure. a, Ribbon representation of GLIC
viewed from the plane of the membrane. DDM molecules bound in
the channel are depicted as yellow sticks plus van der Waals
surface. Horizontal lines represent the membrane limits. b,
Transmembrane part of GLIC viewed from the extracellular side.
The ECD is removed for clarity. Lipids are also depicted in
orange. c, Topology of a GLIC subunit. The conserved core
elements common to GLIC and ELIC are coloured in yellow. d,
Close-up view of the TMD. Only two subunits are represented. The
DDM molecules and the lipids (named LIP601/2/3) close to these
subunits are coloured according to their atomic B-factor (colour
scale at top).
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Figure 3.
Figure 3: Open GLIC and closed ELIC structure comparison. a,
Side view of the structural superposition. For the two subunits
in the foreground, only the common core is depicted, in green
for GLIC, in red for ELIC. Other subunits are in grey. The ECD
rotation axes and the twist axis are depicted. The M4 helix is
omitted for clarity. b, Close-up view of the interface between
the ECD and the TMD (side view in left panel and upper view in
right panel). c, Close-up of transmembrane helices M1–M3
viewed from the channel.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2009,
457,
111-114)
copyright 2009.
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