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PDBsum entry 1mm7

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protein ligands metals Protein-protein interface(s) links
Membrane protein PDB id
1mm7
Jmol
Contents
Protein chains
258 a.a. *
Ligands
QUS ×3
Metals
_ZN ×5
Waters ×774
* Residue conservation analysis
PDB id:
1mm7
Name: Membrane protein
Title: Crystal structure of the glur2 ligand binding core (s1s2j) in complex with quisqualate in a zinc crystal form at 1.65 angstroms resolution
Structure: Glutamate receptor 2. Chain: a, b, c. Fragment: ligand binding core (s1s2j). Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: glur-2 or glur-b. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
1.65Å     R-factor:   0.204     R-free:   0.237
Authors: R.Jin,M.Horning,M.L.Mayer,E.Gouaux
Key ref:
R.Jin et al. (2002). Mechanism of activation and selectivity in a ligand-gated ion channel: structural and functional studies of GluR2 and quisqualate. Biochemistry, 41, 15635-15643. PubMed id: 12501192 DOI: 10.1021/bi020583k
Date:
03-Sep-02     Release date:   04-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19491  (GRIA2_RAT) -  Glutamate receptor 2
Seq:
Struc:
 
Seq:
Struc:
883 a.a.
258 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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: 10.1021/bi020583k Biochemistry 41:15635-15643 (2002)
PubMed id: 12501192  
 
 
Mechanism of activation and selectivity in a ligand-gated ion channel: structural and functional studies of GluR2 and quisqualate.
R.Jin, M.Horning, M.L.Mayer, E.Gouaux.
 
  ABSTRACT  
 
Glutamate is the major excitatory neurotransmitter in the mammalian brain. The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole)propionic acid (AMPA)-subtype glutamate receptor, a ligand-gated ion channel, mediates most of the fast excitatory synaptic transmission in the mammalian central nervous system. Here we present electrophysiological, biochemical, and crystallographic data on the interactions between quisqualate and the GluR2 receptor ion channel and its corresponding ligand binding core. Quisqualate is a high-affinity, full agonist which like AMPA and glutamate elicits maximum peak current responses, and stabilizes the ligand binding core in a fully closed conformation, reinforcing the concept that full agonists produce similar conformational changes [Armstrong, N., and Gouaux, E. (2000) Neuron 28, 165-181]. Nevertheless, the mechanism of quisqualate binding is different from that of AMPA but similar to that of glutamate, illustrating that quisqualate is a faithful glutamate analogue. A detailed comparison of the three agonist complexes reveals distinct binding mechanisms, particularly in the region of a hydrophobic pocket that is proximal to the anionic gamma-substituents, and demonstrates the importance of agonist-water-receptor interactions. The hydrophobic pocket, which is predicted to vary in chemical character between receptor subtypes, probably plays an important role in determining receptor subtype specificity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20457909 J.Gonzalez, M.Du, K.Parameshwaran, V.Suppiramaniam, and V.Jayaraman (2010).
Role of dimer interface in activation and desensitization in AMPA receptors.
  Proc Natl Acad Sci U S A, 107, 9891-9896.  
21080238 T.Nakagawa (2010).
The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors.
  Mol Neurobiol, 42, 161-184.  
19284741 A.H.Ahmed, M.D.Thompson, M.K.Fenwick, B.Romero, A.P.Loh, D.E.Jane, H.Sondermann, and R.E.Oswald (2009).
Mechanisms of antagonism of the GluR2 AMPA receptor: structure and dynamics of the complex of two willardiine antagonists with the glutamate binding domain.
  Biochemistry, 48, 3894-3903.
PDB codes: 3h03 3h06
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
19544581 M.Du, A.Rambhadran, and V.Jayaraman (2009).
Vibrational spectroscopic investigation of the ligand binding domain of kainate receptors.
  Protein Sci, 18, 1585-1591.  
18387631 M.K.Fenwick, and R.E.Oswald (2008).
NMR spectroscopy of the ligand-binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists.
  J Mol Biol, 378, 673-685.  
18491377 T.Mamonova, K.Speranskiy, and M.Kurnikova (2008).
Interplay between structural rigidity and electrostatic interactions in the ligand binding domain of GluR2.
  Proteins, 73, 656-671.  
18823129 T.Mamonova, M.J.Yonkunas, and M.G.Kurnikova (2008).
Energetics of the cleft closing transition and the role of electrostatic interactions in conformational rearrangements of the glutamate receptor ligand binding domain.
  Biochemistry, 47, 11077-11085.  
17337449 A.H.Ahmed, A.P.Loh, D.E.Jane, and R.E.Oswald (2007).
Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy.
  J Biol Chem, 282, 12773-12784.  
16892196 D.Catarzi, V.Colotta, and F.Varano (2007).
Competitive AMPA receptor antagonists.
  Med Res Rev, 27, 239-278.  
17260963 K.A.Mankiewicz, A.Rambhadran, M.Du, G.Ramanoudjame, and V.Jayaraman (2007).
Role of the chemical interactions of the agonist in controlling alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation.
  Biochemistry, 46, 1343-1349.  
17934637 K.A.Mankiewicz, and V.Jayaraman (2007).
Glutamate receptors as seen by light: spectroscopic studies of structure-function relationships.
  Braz J Med Biol Res, 40, 1419-1427.  
17545169 W.Pei, M.Ritz, M.McCarthy, Z.Huang, and L.Niu (2007).
Receptor occupancy and channel-opening kinetics: a study of GLUR1 L497Y AMPA receptor.
  J Biol Chem, 282, 22731-22736.  
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.  
16731549 W.Zhang, A.Robert, S.B.Vogensen, and J.R.Howe (2006).
The relationship between agonist potency and AMPA receptor kinetics.
  Biophys J, 91, 1336-1346.  
15996549 A.Inanobe, H.Furukawa, and E.Gouaux (2005).
Mechanism of partial agonist action at the NR1 subunit of NMDA receptors.
  Neuron, 47, 71-84.
PDB codes: 1y1m 1y1z 1y20
15794751 B.B.Nielsen, D.S.Pickering, J.R.Greenwood, L.Brehm, M.Gajhede, A.Schousboe, and J.S.Kastrup (2005).
Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP.
  FEBS J, 272, 1639-1648.
PDB code: 1wvj
16281028 H.Furukawa, S.K.Singh, R.Mancusso, and E.Gouaux (2005).
Subunit arrangement and function in NMDA receptors.
  Nature, 438, 185-192.
PDB codes: 2a5s 2a5t 2ipv
15721240 M.L.Mayer (2005).
Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity.
  Neuron, 45, 539-552.
PDB codes: 1s50 1s7y 1s9t 1sd3 1tt1 1txf
16099829 M.M.Holm, M.L.Lunn, S.F.Traynelis, J.S.Kastrup, and J.Egebjerg (2005).
Structural determinants of agonist-specific kinetics at the ionotropic glutamate receptor 2.
  Proc Natl Acad Sci U S A, 102, 12053-12058.  
14610080 G.Li, and L.Niu (2004).
How fast does the GluR1Qflip channel open?
  J Biol Chem, 279, 3990-3997.  
15224382 K.Strømgaard, and I.Mellor (2004).
AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins.
  Med Res Rev, 24, 589-620.  
15184361 M.B.Hermit, J.R.Greenwood, and H.Bräuner-Osborne (2004).
Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues.
  J Biol Chem, 279, 34811-34817.  
15229875 M.Kubo, and E.Ito (2004).
Structural dynamics of an ionotropic glutamate receptor.
  Proteins, 56, 411-419.  
14977400 M.L.Mayer, and N.Armstrong (2004).
Structure and function of glutamate receptor ion channels.
  Annu Rev Physiol, 66, 161-181.  
14766177 M.S.Horning, and M.L.Mayer (2004).
Regulation of AMPA receptor gating by ligand binding core dimers.
  Neuron, 41, 379-388.  
14567698 G.Li, R.E.Oswald, and L.Niu (2003).
Channel-opening kinetics of GluR6 kainate receptor.
  Biochemistry, 42, 12367-12375.  
14567697 G.Li, W.Pei, and L.Niu (2003).
Channel-opening kinetics of GluR2Q(flip) AMPA receptor: a laser-pulse photolysis study.
  Biochemistry, 42, 12358-12366.  
12805203 H.Furukawa, and E.Gouaux (2003).
Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core.
  EMBO J, 22, 2873-2885.
PDB codes: 1pb7 1pb8 1pb9 1pbq
12730367 N.Armstrong, M.Mayer, and E.Gouaux (2003).
Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes.
  Proc Natl Acad Sci U S A, 100, 5736-5741.
PDB codes: 1p1n 1p1o 1p1q 1p1u 1p1w
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.