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PDBsum entry 4u23
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Transport protein, membrane protein
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PDB id
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4u23
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References listed in PDB file
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Key reference
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Title
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Structure and dynamics of ampa receptor glua2 in resting, Pre-Open, And desensitized states.
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Authors
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K.L.Dürr,
L.Chen,
R.A.Stein,
R.De zorzi,
I.M.Folea,
T.Walz,
H.S.Mchaourab,
E.Gouaux.
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Ref.
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Cell, 2014,
158,
778-792.
[DOI no: ]
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PubMed id
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Abstract
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Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory
signaling in the nervous system. Despite the profound importance of iGluRs to
neurotransmission, little is known about the structures and dynamics of intact
receptors in distinct functional states. Here, we elucidate the structures of
the intact GluA2 AMPA receptor in an apo resting/closed state, in an
activated/pre-open state bound with partial agonists and a positive allosteric
modulator, and in a desensitized/closed state in complex with
fluorowilliardiine. To probe the conformational properties of these states, we
carried out double electron-electron resonance experiments on cysteine mutants
and cryoelectron microscopy studies. We show how agonist binding modulates the
conformation of the ligand-binding domain "layer" of the intact
receptors and how, upon desensitization, the receptor undergoes large
conformational rearrangements of the amino-terminal and ligand-binding domains.
We define mechanistic principles by which to understand antagonism, activation,
and desensitization in AMPA iGluRs.
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