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PDBsum entry 3ij4
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Transport protein
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PDB id
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3ij4
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References listed in PDB file
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Key reference
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Title
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Pore architecture and ion sites in acid-Sensing ion channels and p2X receptors.
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Authors
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E.B.Gonzales,
T.Kawate,
E.Gouaux.
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Ref.
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Nature, 2009,
460,
599-604.
[DOI no: ]
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PubMed id
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Abstract
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Acid-sensing ion channels are proton-activated, sodium-selective channels
composed of three subunits, and are members of the superfamily of epithelial
sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels.
These ubiquitous eukaryotic ion channels have essential roles in biological
activities as diverse as sodium homeostasis, taste and pain. Despite their
crucial roles in biology and their unusual trimeric subunit stoichiometry, there
is little knowledge of the structural and chemical principles underlying their
ion channel architecture and ion-binding sites. Here we present the structure of
a functional acid-sensing ion channel in a desensitized state at 3 A resolution,
the location and composition of the approximately 8 A 'thick' desensitization
gate, and the trigonal antiprism coordination of caesium ions bound in the
extracellular vestibule. Comparison of the acid-sensing ion channel structure
with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and
aqueous vestibules, suggesting that there are unanticipated yet common
structural and mechanistic principles.
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Figure 2.
Figure 2: Structure of ASIC1mfc. a, View of the functional
ASIC1mfc trimer. Chloride ions are green spheres. The 'thumb',
'finger' and wrist regions are labelled. Grey bars suggest the
boundaries of the outer (out) and inner (in) leaflets of the
membrane bilayer. b, A vertical slice through a
solvent-accessible surface representation of the transmembrane
domain, the extracellular vestibule and fenestrations. One of
the three equivalent fenestrations is indicated by an arrow. Asp
433 defines the bottom of the extracellular vestibule. c, Key
interactions between symmetry-related Asp 433 carboxyl and Tyr
425 hydroxyl groups.
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Figure 4.
Figure 4: Cs^+-binding sites. a, Stereo image of the electron
density peaks (3.5 )
from anomalous difference Fourier maps calculated using
diffraction data measured from crystals soaked in CsCl. b, Key
interactions between Cs^+ ions at sites 1 and 2 with the
main-chain and side-chain oxygen atoms of Gly 432 and Asp 433,
respectively. c, Stick representation of ASIC1mfc interaction
with Cs^+ at site 2. d, Trigonal antiprism coordination of the
Cs^+ ion by the Gly 432 carbonyl and Asp 433 carboxyl oxygens.
Oxygen atoms (red spheres) form the vertices, whereas solid
lines represent the sides of each of the two staggered triangles
of the antiprism.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2009,
460,
599-604)
copyright 2009.
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