The pore domain in glutamate-gated ion channels: Structure, drug binding and similarity with potassium channels

Ionotropic glutamate receptors in the CNS excitatory synapses of vertebrates are involved in numerous physiological and pathological processes. Decades of intensive studies greatly advanced our understanding of molecular organization of these transmembrane proteins. Here we focus on the channel pore...

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Published inBiochimica et biophysica acta. Biomembranes Vol. 1862; no. 10; p. 183401
Main Authors Tikhonov, Denis B., Zhorov, Boris S.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.10.2020
Subjects
Amino Acid Sequence
AMPA channels
Channel block
Cryo-EM structures
Cryoelectron Microscopy
Crystal structures
Glutamic Acid - physiology
Ion Channel Gating - physiology
Ionotropic glutamate receptors
Molecular modeling
NMDA channels
Potassium Channels - chemistry
Potassium Channels - metabolism
Protein Conformation
Sequence Homology, Amino Acid
Crystal structures
iGluR
AMPA
NMDA channels
Ionotropic glutamate receptors
AMPAR
Channel block
PDB
AMPA channels
Cryo-EM structures
Molecular modeling
NMDA
NMDAR
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Summary:Ionotropic glutamate receptors in the CNS excitatory synapses of vertebrates are involved in numerous physiological and pathological processes. Decades of intensive studies greatly advanced our understanding of molecular organization of these transmembrane proteins. Here we focus on the channel pore domain, its selectivity filter and the activation gate, and the pore block by organic ligands. We compare findings from indirect experimental approaches, including site-directed mutagenesis, with recent crystal and cryo-EM structures of different channels in different functional states and complexed with different ligands. We summarize remaining uncertainties and unresolved problems related to the channel structure, function and pharmacology. •Crystal and cryo-EM structures of iGluR channels advanced knowledge of their atomic mechanisms•The pore domain structures of iGlur and K channels are similar•The structures shed light on the selectivity filter, but not on the pore block mechanism•iGlur gating involves movement of the inner helices and, possibly, changes at the selectivity filter•PDB-deposited structures require critical analysis in view of other data
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0005-2736
1879-2642
1879-2642
DOI:10.1016/j.bbamem.2020.183401