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PDBsum entry 4l17
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Transport protein
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PDB id
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4l17
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References listed in PDB file
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Key reference
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Title
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A conformational intermediate in glutamate receptor activation.
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Authors
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A.Y.Lau,
H.Salazar,
L.Blachowicz,
V.Ghisi,
A.J.Plested,
B.Roux.
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Ref.
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Neuron, 2013,
79,
492-503.
[DOI no: ]
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PubMed id
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Abstract
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Ionotropic glutamate receptors (iGluRs) transduce the chemical signal of
neurotransmitter release into membrane depolarization at excitatory synapses in
the brain. The opening of the transmembrane ion channel of these ligand-gated
receptors is driven by conformational transitions that are induced by the
association of glutamate molecules to the ligand-binding domains (LBDs). Here,
we describe the crystal structure of a GluA2 LBD tetramer in a configuration
that involves an ∼30° rotation of the LBD dimers relative to the crystal
structure of the full-length receptor. The configuration is stabilized by an
engineered disulfide crosslink. Biochemical and electrophysiological studies on
full-length receptors incorporating either this crosslink or an engineered metal
bridge show that this LBD configuration corresponds to an intermediate state of
receptor activation. GluA2 activation therefore involves a combination of both
intra-LBD (cleft closure) and inter-LBD dimer conformational transitions.
Overall, these results provide a comprehensive structural characterization of an
iGluR intermediate state.
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