PDBsum entry 2i0b

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Membrane protein PDB id
Protein chains
254 a.a. *
GLU ×3
Waters ×538
* Residue conservation analysis
PDB id:
Name: Membrane protein
Title: Crystal structure of the glur6 ligand binding core elkq muta at 1.96 angstroms resolution
Structure: Glutamate receptor, ionotropic kainate 2. Chain: a, b, c. Synonym: glutamate receptor 6, glur-6, glur6. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: grik2, glur6. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.96Å     R-factor:   0.174     R-free:   0.211
Authors: M.L.Mayer
Key ref:
M.C.Weston et al. (2006). Conformational restriction blocks glutamate receptor desensitization. Nat Struct Mol Biol, 13, 1120-1127. PubMed id: 17115050 DOI: 10.1038/nsmb1178
10-Aug-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P42260  (GRIK2_RAT) -  Glutamate receptor ionotropic, kainate 2
908 a.a.
254 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biochemical function     ionotropic glutamate receptor activity     2 terms  


DOI no: 10.1038/nsmb1178 Nat Struct Mol Biol 13:1120-1127 (2006)
PubMed id: 17115050  
Conformational restriction blocks glutamate receptor desensitization.
M.C.Weston, P.Schuck, A.Ghosal, C.Rosenmund, M.L.Mayer.
Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not by engineering the dimer interface. Crystallographic analysis of the GluR6 Y490C L752C dimer revealed relaxation from the active conformation, which functional studies reveal is not sufficient to trigger desensitization. The equivalent non-desensitizing cross-linked GluR2 mutant retained weak sensitivity to a positive allosteric modulator, which had no effect on GluR2 L483Y. These results establish that the active conformation of AMPA and kainate receptors is conserved and further show that their desensitization requires dimer rearrangements, that subtle structural differences account for their diverse functional properties and that the ligand-binding core dimer is a powerful regulator of ion-channel activity.
  Selected figure(s)  
Figure 4.
Figure 4. Non-desensitizing glutamate receptors created by ligand-binding core disulfide bond cross-links. Responses to 10 mM glutamate, recorded from outside-out patches from HEK cells transfected with the indicated cDNA species, are shown for wild-type GluR2 and the kainate receptors GluR5, GluR6 and GluR7 (left charts) and for their ligand-binding core double cysteine mutants (right charts). Upper traces in each panel show open-tip responses recorded at the end of the experiment.
Figure 6.
Figure 6. Analysis of disulfide bond–cross-linked receptors. (a) Crystal structure of the GluR6 Y490C L752C mutant cross-linked dimer assembly. C positions of Ser761 and Ile653 are show as black spheres at the top and bottom of each subunit, respectively. (b) Electron density for [A]-weighted F[o] – F[c] omit maps at 2.25-Å resolution, contoured at 3.25 calculated with the Y490C L752C residues omitted from the F[c] calculation. (c) Crystal structure of the GluR6 ELKQ mutant dimer, illustrating the change in separation of Ser761 and Ile653 compared with the disulfide bond–cross-linked receptor. (d) Superimposed responses to 10 mM glutamate (black bars above traces) recorded in the absence or presence of cyclothiazide (white bar; asterisks mark traces in the presence of cyclothiazide), from outside-out patches from HEK cells transfected with cDNAs for GluR2 L483C L752C (left) and GluR2 L483Y (right).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 1120-1127) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21372852 M.L.Mayer (2011).
Glutamate receptor ion channels: where do all the calories go?
  Nat Struct Mol Biol, 18, 253-254.  
21349697 M.L.Mayer (2011).
Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.
  Curr Opin Neurobiol, 21, 283-290.  
20850188 D.Perrais, J.Veran, and C.Mulle (2010).
Gating and permeation of kainate receptors: differences unveiled.
  Trends Pharmacol Sci, 31, 516-522.  
20404149 U.Das, J.Kumar, M.L.Mayer, and A.J.Plested (2010).
Domain organization and function in GluK2 subtype kainate receptors.
  Proc Natl Acad Sci U S A, 107, 8463-8468.  
19946266 A.I.Sobolevsky, M.P.Rosconi, and E.Gouaux (2009).
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor.
  Nature, 462, 745-756.
PDB codes: 3kg2 3kgc
19617541 C.Chaudhry, A.J.Plested, P.Schuck, and M.L.Mayer (2009).
Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions.
  Proc Natl Acad Sci U S A, 106, 12329-12334.  
19339989 C.Chaudhry, M.C.Weston, P.Schuck, C.Rosenmund, and M.L.Mayer (2009).
Stability of ligand-binding domain dimer assembly controls kainate receptor desensitization.
  EMBO J, 28, 1518-1530.
PDB codes: 3g3f 3g3g 3g3h 3g3i 3g3j 3g3k
19793963 H.Yuan, K.B.Hansen, K.M.Vance, K.K.Ogden, and S.F.Traynelis (2009).
Control of NMDA receptor function by the NR2 subunit amino-terminal domain.
  J Neurosci, 29, 12045-12058.  
19465914 J.Kumar, P.Schuck, R.Jin, and M.L.Mayer (2009).
The N-terminal domain of GluR6-subtype glutamate receptor ion channels.
  Nat Struct Mol Biol, 16, 631-638.
PDB codes: 3h6g 3h6h
19176800 K.B.Hansen, P.Naur, N.L.Kurtkaya, A.S.Kristensen, M.Gajhede, J.S.Kastrup, and S.F.Traynelis (2009).
Modulation of the dimer interface at ionotropic glutamate-like receptor delta2 by D-serine and extracellular calcium.
  J Neurosci, 29, 907-917.  
19297335 K.Frydenvang, L.L.Lash, P.Naur, P.A.Postila, D.S.Pickering, C.M.Smith, M.Gajhede, M.Sasaki, R.Sakai, O.T.Pentikaïnen, G.T.Swanson, and J.S.Kastrup (2009).
Full Domain Closure of the Ligand-binding Core of the Ionotropic Glutamate Receptor iGluR5 Induced by the High Affinity Agonist Dysiherbaine and the Functional Antagonist 8,9-Dideoxyneodysiherbaine.
  J Biol Chem, 284, 14219-14229.
PDB codes: 3gba 3gbb
19561126 N.Nayeem, Y.Zhang, D.K.Schweppe, D.R.Madden, and T.Green (2009).
A nondesensitizing kainate receptor point mutant.
  Mol Pharmacol, 76, 534-542.  
17947494 D.E.Featherstone, and S.A.Shippy (2008).
Regulation of synaptic transmission by ambient extracellular glutamate.
  Neuroscientist, 14, 171-181.  
18184566 M.Gielen, A.Le Goff, D.Stroebel, J.W.Johnson, J.Neyton, and P.Paoletti (2008).
Structural rearrangements of NR1/NR2A NMDA receptors during allosteric inhibition.
  Neuron, 57, 80-93.  
18636091 Y.Yao, C.B.Harrison, P.L.Freddolino, K.Schulten, and M.L.Mayer (2008).
Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors.
  EMBO J, 27, 2158-2170.
PDB codes: 2rc7 2rc8 2rc9 2rca 2rcb
17359918 A.J.Plested, and M.L.Mayer (2007).
Structure and mechanism of kainate receptor modulation by anions.
  Neuron, 53, 829-841.
PDB code: 2ojt
17581823 H.Hald, P.Naur, D.S.Pickering, D.Sprogøe, U.Madsen, D.B.Timmermann, P.K.Ahring, T.Liljefors, A.Schousboe, J.Egebjerg, M.Gajhede, and J.S.Kastrup (2007).
Partial agonism and antagonism of the ionotropic glutamate receptor iGLuR5: structures of the ligand-binding core in complex with domoic acid and 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid.
  J Biol Chem, 282, 25726-25736.
PDB codes: 1vso 2pbw
17629578 I.H.Greger, E.B.Ziff, and A.C.Penn (2007).
Molecular determinants of AMPA receptor subunit assembly.
  Trends Neurosci, 30, 407-416.  
17208968 N.A.Mitchell, and M.W.Fleck (2007).
Targeting AMPA receptor gating processes with allosteric modulators and mutations.
  Biophys J, 92, 2392-2402.  
17178406 A.Priel, S.Selak, J.Lerma, and Y.Stern-Bach (2006).
Block of kainate receptor desensitization uncovers a key trafficking checkpoint.
  Neuron, 52, 1037-1046.  
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.