PDBsum entry 1syi

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Membrane protein PDB id
Protein chains
259 a.a. *
CPW ×2
Waters ×372
* Residue conservation analysis
PDB id:
Name: Membrane protein
Title: X-ray structure of the y702f mutant of the glur2 ligand- binding core (s1s2j) in complex with (s)-cpw399 at 2.1 a resolution.
Structure: Glutamate receptor 2. Chain: a, b. Fragment: glur2-flop ligand-binding core (s1s2j). Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gria2, glur2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.206     R-free:   0.254
Authors: A.Frandsen,D.S.Pickering,B.Vestergaard,C.Kasper,B.B.Nielsen, J.R.Greenwood,G.Campiani,M.Gajhede,A.Schousboe,J.S.Kastrup
Key ref: A.Frandsen et al. (2005). Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2. Mol Pharmacol, 67, 703-713. PubMed id: 15591246 DOI: 10.1124/mol.104.002931
01-Apr-04     Release date:   22-Mar-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19491  (GRIA2_RAT) -  Glutamate receptor 2
883 a.a.
259 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transport   1 term 
  Biochemical function     transporter activity     3 terms  


DOI no: 10.1124/mol.104.002931 Mol Pharmacol 67:703-713 (2005)
PubMed id: 15591246  
Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2.
A.Frandsen, D.S.Pickering, B.Vestergaard, C.Kasper, B.B.Nielsen, J.R.Greenwood, G.Campiani, C.Fattorusso, M.Gajhede, A.Schousboe, J.S.Kastrup.
Ionotropic glutamate receptors mediate most rapid excitatory synaptic transmission in the mammalian central nervous system, and their involvement in neurological diseases has stimulated widespread interest in their structure and function. Despite a large number of agonists developed so far, few display selectivity among (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA)-receptor subtypes. The present study provides X-ray structures of the glutamate receptor 2 (GluR2)-selective partial agonist (S)-2-amino-3-(1,3,5,6,7-pentahydro-2,4-dioxocyclopenta[e] pyrimidin-1-yl) propanoic acid [(S)-CPW399] in complex with the ligand-binding core of GluR2 (GluR2-S1S2J) and with a (Y702F)GluR2-S1S2J mutant. In addition, the structure of the nonselective partial agonist kainate in complex with (Y702F)GluR2-S1S2J was determined. The results show that the selectivity of (S)-CPW399 toward full-length GluR2 relative to GluR3 is reflected in the binding data on the two soluble constructs, allowing the use of (Y702F)GluR2-S1S2J as a model system for studying GluR2/GluR3 selectivity. Structural comparisons suggest that selectivity arises from disruption of a water-mediated network between ligand and receptor. A D1-D2 domain closure occurs upon agonist binding. (S)-CPW399 and kainate induce greater domain closure in the Y702F mutant, indicating that these partial agonists here act in a manner more reminiscent of full agonists. Both kainate and (S)-CPW399 exhibited higher efficacy at (Y702F)GluR2(Q)i than at wild-type GluR2(Q)i. Whereas an excellent correlation exists between domain closure and efficacy of a range of agonists at full-length GluR2 determined by electrophysiology in Xenopus laevis oocytes, a direct correlation between agonist induced domain closure of (Y702F)GluR2-S1S2J and efficacy at the GluR3 receptor is not observed. Although it clearly controls selectivity, mutation of this residue alone is insufficient to explain agonist-induced conformational rearrangements occurring in this variant.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21516102 A.S.Kristensen, M.A.Jenkins, T.G.Banke, A.Schousboe, Y.Makino, R.C.Johnson, R.Huganir, and S.F.Traynelis (2011).
Mechanism of Ca(2+)/calmodulin-dependent kinase II regulation of AMPA receptor gating.
  Nat Neurosci, 14, 727-735.  
20713069 J.Pøhlsgaard, K.Frydenvang, U.Madsen, and J.S.Kastrup (2011).
Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators.
  Neuropharmacology, 60, 135-150.  
18623169 L.Bunch, and P.Krogsgaard-Larsen (2009).
Subtype selective kainic acid receptor agonists: discovery and approaches to rational design.
  Med Res Rev, 29, 3.  
19102704 A.Gill, A.Birdsey-Benson, B.L.Jones, L.P.Henderson, and D.R.Madden (2008).
Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists.
  Biochemistry, 47, 13831-13841.
PDB codes: 3en3 3epe
18214958 E.J.Bjerrum, and P.C.Biggin (2008).
Rigid body essential X-ray crystallography: distinguishing the bend and twist of glutamate receptor ligand binding domains.
  Proteins, 72, 434-446.  
19019243 M.J.Cuneo, L.S.Beese, and H.W.Hellinga (2008).
Ligand-induced conformational changes in a thermophilic ribose-binding protein.
  BMC Struct Biol, 8, 50.
PDB codes: 2fn8 2fn9
18022568 B.H.Kaae, K.Harpsøe, J.S.Kastrup, A.C.Sanz, D.S.Pickering, B.Metzler, R.P.Clausen, M.Gajhede, P.Sauerberg, T.Liljefors, and U.Madsen (2007).
Structural proof of a dimeric positive modulator bridging two identical AMPA receptor-binding sites.
  Chem Biol, 14, 1294-1303.
PDB code: 3bbr
16474411 P.E.Chen, and D.J.Wyllie (2006).
Pharmacological insights obtained from structure-function studies of ionotropic glutamate receptors.
  Br J Pharmacol, 147, 839-853.  
15919192 M.L.Mayer (2005).
Glutamate receptor ion channels.
  Curr Opin Neurobiol, 15, 282-288.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.