2XXX
Crystal structure of the GluK2 (GluR6) D776K LBD dimer in complex with glutamate (P21 21 21)
Summary for 2XXX
| Entry DOI | 10.2210/pdb2xxx/pdb |
| Related | 1S50 1S7Y 1S9T 1SD3 1TT1 1YAE 2I0B 2I0C 2XXR 2XXT 2XXU 2XXV 2XXW 2XXY |
| Descriptor | GLUTAMATE RECEPTOR, IONOTROPIC KAINATE 2, GLUTAMIC ACID (3 entities in total) |
| Functional Keywords | transport protein |
| Biological source | RATTUS NORVEGICUS (NORWAY RAT) |
| Total number of polymer chains | 4 |
| Total formula weight | 119148.66 |
| Authors | Nayeem, N.,Mayans, O.,Green, T. (deposition date: 2010-11-12, release date: 2011-02-09, Last modification date: 2023-12-20) |
| Primary citation | Nayeem, N.,Mayans, O.,Green, T. Conformational Flexibility of the Ligand-Binding Domain Dimer in Kainate Receptor Gating and Desensitization J.Neurosci., 31:2916-, 2011 Cited by PubMed Abstract: AMPA- and kainate (KA)-selective ionotropic glutamate receptors (iGluRs) respond to agonist by opening (gating), then closing (desensitizing) in quick succession. Gating has been linked to agonist-induced changes within the ligand-binding domain (LBD), and desensitization to rearrangement of a dimer formed by neighboring LBDs. To explore the role of dimer conformation in both gating and desensitization, we compared the conformational effects of two kainate receptor mutants. The first, GluK2-D776K, blocks desensitization of macroscopic current responses ("macroscopic desensitization"). The second, GluK2-M770K, accelerates macroscopic desensitization and eliminates the effects of external ions on channel kinetics. Using structures determined by x-ray crystallography, we found that in both mutants the introduced lysines act as tethered cations, displacing sodium ions from their binding sites within the dimer interface. This results in new inter- and intra-protomer contacts in D776K and M770K respectively, explaining the effects of these mutations on dimer stability and desensitization kinetics. Further, chloride binding was unaffected by the M770K mutation, even though binding of sodium ions has been proposed to promote dimer stability by stabilizing anion binding. This suggests sodium binding may affect receptor function more directly than currently supposed. Notably, we also observed a ligand-specific shift in dimer conformation when comparing LBD dimers in complex with glutamate or the partial agonist KA, revealing a previously unidentified role for dimer orientation in iGluR gating. PubMed: 21414913DOI: 10.1523/JNEUROSCI.4771-10.2011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.098 Å) |
Structure validation
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