| http://purl.uniprot.org/citations/12730367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12730367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12730367 | http://www.w3.org/2000/01/rdf-schema#comment | "The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole) propionic acid (AMPA) receptor discriminates between agonists in terms of binding and channel gating; AMPA is a high-affinity full agonist, whereas kainate is a low-affinity partial agonist. Although there is extensive literature on the functional characterization of partial agonist activity in ion channels, structure-based mechanisms are scarce. Here we investigate the role of Leu-650, a binding cleft residue conserved among AMPA receptors, in maintaining agonist specificity and regulating agonist binding and channel gating by using physiological, x-ray crystallographic, and biochemical techniques. Changing Leu-650 to Thr yields a receptor that responds more potently and efficaciously to kainate and less potently and efficaciously to AMPA relative to the WT receptor. Crystal structures of the Leu-650 to Thr mutant reveal an increase in domain closure in the kainate-bound state and a partially closed and a fully closed conformation in the AMPA-bound form. Our results indicate that agonists can induce a range of conformations in the GluR2 ligand-binding core and that domain closure is directly correlated to channel activation. The partially closed, AMPA-bound conformation of the L650T mutant likely captures the structure of an agonist-bound, inactive state of the receptor. Together with previously solved structures, we have determined a mechanism of agonist binding and subsequent conformational rearrangements."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1037393100"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1037393100"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Gouaux E."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Gouaux E."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Mayer M."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Mayer M."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Armstrong N."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/author | "Armstrong N."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/pages | "5736-5741"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/pages | "5736-5741"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/title | "Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/title | "Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes."xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/volume | "100"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://purl.uniprot.org/core/volume | "100"xsd:string |
| http://purl.uniprot.org/citations/12730367 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12730367 |
| http://purl.uniprot.org/citations/12730367 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12730367 |
| http://purl.uniprot.org/citations/12730367 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12730367 |
| http://purl.uniprot.org/citations/12730367 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12730367 |