Domain interactions regulating ampa receptor desensitization.
Desensitization is a common property of glutamate and other ligand-gated ion channels, yet its molecular mechanism is unknown. For glutamate receptors, agonist binding involves interactions with identified amino acids from two lobes and may result in stabilizing the lobes in a closed "clamshell" conformation. The present studies demonstrate that two structures, beta-strands 7 and 8 and alpha-helices J and K, functionally interact with each other and likely form hinges between the two lobes, influencing the coupling between agonist binding and desensitization. Two amino acids identified within these regions form a solvent-exposed interface with a third amino acid, a mutation of which was shown previously to block receptor desensitization (L(507) in glutamate receptor 3). This interface may regulate a concerted conformational shift of the AMPA subtype of glutamate receptor subunits to the desensitized state.
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523-1670, USA. kpartin@lamar.colostate.edu
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D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017433:Protein Structure, Secondary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014981:Xenopus; D000097806:GluK2 Kainate Receptor
D001581:Benzothiadiazines; D021122:Protein Subunits; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011993:Recombinant Fusion Proteins; D000097806:GluK2 Kainate Receptor; C104723:glutamate receptor ionotropic, AMPA 3; C004639:cyclothiazide