| Structural highlights
4bdl is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1s50, 1s7y, 1s9t, 1sd3, 1tt1, 1yae, 2i0b, 2i0c, 2xxr, 2xxt, 2xxu, 2xxv, 2xxw, 2xxx, 2xxy, 4bdm, 4bdn, 4bdo, 4bdp, 4bdq, 4bdr |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GRIK2_RAT] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity).[1] [2]
Publication Abstract from PubMed
Gating of AMPA- and kainate-selective ionotropic glutamate receptors can be defined in terms of ligand affinity, efficacy and the rate and extent of desensitization. Crucial insights into all three elements have come from structural studies of the ligand-binding domain (LBD). In particular, binding-cleft closure is associated with efficacy, whereas dissociation of the dimer formed by neighbouring LBDs is linked with desensitization. We have explored these relationships in the kainate-selective subunit GluK2 by studying the effects of mutating two residues (K531 and R775) that form key contacts within the LBD dimer interface, but whose truncation unexpectedly attenuates desensitization. One mutation (K531A) also switches the relative efficacies of glutamate and kainate. LBD crystal structures incorporating these mutations revealed several conformational changes that together explain their phenotypes. K531 truncation results in new dimer contacts, consistent with slower desensitization and sideways movement in the ligand-binding cleft correlating with efficacy. The tested mutants also disrupted anion binding; no chloride was detected in the dimer-interface site, including in R775A where absence of chloride was the only structural change evident. From this, we propose that the charge balance in the GluK2 LBD dimer interface maintains a degree of instability, necessary for rapid and complete desensitization.
Correlating efficacy and desensitization with GluK2 ligand-binding domain movements.,Nayeem N, Mayans O, Green T Open Biol. 2013 May 29;3(5):130051. doi: 10.1098/rsob.130051. PMID:23720540[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martin S, Nishimune A, Mellor JR, Henley JM. SUMOylation regulates kainate-receptor-mediated synaptic transmission. Nature. 2007 May 17;447(7142):321-5. Epub 2007 May 7. PMID:17486098 doi:nature05736
- ↑ Weston MC, Schuck P, Ghosal A, Rosenmund C, Mayer ML. Conformational restriction blocks glutamate receptor desensitization. Nat Struct Mol Biol. 2006 Dec;13(12):1120-7. Epub 2006 Nov 19. PMID:17115050 doi:http://dx.doi.org/10.1038/nsmb1178
- ↑ Nayeem N, Mayans O, Green T. Correlating efficacy and desensitization with GluK2 ligand-binding domain movements. Open Biol. 2013 May 29;3(5):130051. doi: 10.1098/rsob.130051. PMID:23720540 doi:10.1098/rsob.130051
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