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PDBsum entry 2gfe
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protein ligands metals Protein-protein interface(s) links
Membrane protein PDB id
2gfe

 

 

 

 

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Contents
Protein chains
260 a.a. *
Ligands
GLU ×3
Metals
_ZN ×5
Waters ×746
* Residue conservation analysis
PDB id:
2gfe
Name: Membrane protein
Title: Crystal structure of the glur2 a476e s673d ligand binding core mutant at 1.54 angstroms resolution
Structure: Glutamate receptor 2. Chain: a, b, c. Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2, ampa-selective glutamate receptor 2. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gria2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.54Å     R-factor:   0.213     R-free:   0.227
Authors: M.L.Mayer
Key ref: M.C.Weston et al. (2006). Interdomain interactions in AMPA and kainate receptors regulate affinity for glutamate. J Neurosci, 26, 7650-7658. PubMed id: 16855092
Date:
21-Mar-06     Release date:   22-Aug-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		883 a.a.
260 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 

 
J Neurosci 26:7650-7658 (2006)
PubMed id: 16855092  
 
 
Interdomain interactions in AMPA and kainate receptors regulate affinity for glutamate.
M.C.Weston, C.Gertler, M.L.Mayer, C.Rosenmund.
 
  ABSTRACT  
 
Ionotropic glutamate receptors perform diverse functions in the nervous system. As a result, multiple receptor subtypes have evolved with different kinetics, ion permeability, expression patterns, and regulation by second messengers. Kainate receptors show slower recovery from desensitization and have different affinities for agonists than AMPA receptors. Based on analysis of ligand binding domain crystal structures, we identified interdomain interactions in the agonist-bound state that are conserved in kainate receptors and absent in AMPA receptors. Mutations in GluR6 designed to disrupt these contacts reduced agonist apparent affinity, speeded up receptor deactivation and increased the rate of recovery from desensitization. Conversely, introduction of mutations in GluR2 that enabled additional interdomain interactions in the agonist-bound state increased agonist apparent affinity 15-fold, and slowed both deactivation and recovery from desensitization. We conclude that interdomain interactions have evolved as a distinct mechanism that contributes to the unique kinetic properties of AMPA and kainate receptors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22948927 S.S.Cha, Y.J.An, C.S.Jeong, M.K.Kim, S.G.Lee, K.H.Lee, and B.H.Oh (2012).
Experimental phasing using zinc anomalous scattering.
  Acta Crystallogr D Biol Crystallogr, 68, 1253-1258.
PDB codes: 4dt3 4dwz 4fc5
21317895 A.Y.Lau, and B.Roux (2011).
The hidden energetics of ligand binding and activation in a glutamate receptor.
  Nat Struct Mol Biol, 18, 283-287.  
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.  
  21522138 K.M.Vance, N.Simorowski, S.F.Traynelis, and H.Furukawa (2011).
Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors.
  Nat Commun, 2, 294.
PDB codes: 3oek 3oel 3oem 3oen
  21395862 P.Paoletti (2011).
Molecular basis of NMDA receptor functional diversity.
  Eur J Neurosci, 33, 1351-1365.  
20850188 D.Perrais, J.Veran, and C.Mulle (2010).
Gating and permeation of kainate receptors: differences unveiled.
  Trends Pharmacol Sci, 31, 516-522.  
20185686 J.von Engelhardt, V.Mack, R.Sprengel, N.Kavenstock, K.W.Li, Y.Stern-Bach, A.B.Smit, P.H.Seeburg, and H.Monyer (2010).
CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus.
  Science, 327, 1518-1522.  
20299582 M.Farrant, and S.G.Cull-Candy (2010).
Neuroscience. AMPA receptors--another twist?
  Science, 327, 1463-1465.  
20877838 R.Edwards, J.Madine, L.Fielding, and D.A.Middleton (2010).
Measurement of multiple torsional angles from one-dimensional solid-state NMR spectra: application to the conformational analysis of a ligand in its biological receptor site.
  Phys Chem Chem Phys, 12, 13999-14008.  
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
19506248 S.M.Schmid, S.Kott, C.Sager, T.Huelsken, and M.Hollmann (2009).
The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation.
  Proc Natl Acad Sci U S A, 106, 10320-10325.  
18923416 A.C.Penn, S.R.Williams, and I.H.Greger (2008).
Gating motions underlie AMPA receptor secretion from the endoplasmic reticulum.
  EMBO J, 27, 3056-3068.  
18549784 A.J.Plested, R.Vijayan, P.C.Biggin, and M.L.Mayer (2008).
Molecular basis of kainate receptor modulation by sodium.
  Neuron, 58, 720-735.
PDB codes: 3c31 3c32 3c33 3c34 3c35 3c36
18450751 M.L.Blanke, and A.M.VanDongen (2008).
Constitutive activation of the N-methyl-D-aspartate receptor via cleft-spanning disulfide bonds.
  J Biol Chem, 283, 21519-21529.  
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.  
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
17884024 K.Montgomery, E.Suzuki, M.Kessler, and A.C.Arai (2007).
Factors affecting guanine nucleotide binding to rat AMPA receptors.
  Brain Res, 1177, 1-8.  
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.  
17115050 M.C.Weston, P.Schuck, A.Ghosal, C.Rosenmund, and M.L.Mayer (2006).
Conformational restriction blocks glutamate receptor desensitization.
  Nat Struct Mol Biol, 13, 1120-1127.
PDB codes: 2i0b 2i0c
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.

 

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