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PDBsum entry 3b6w

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protein ligands Protein-protein interface(s) links
Membrane protein PDB id
3b6w
Jmol
Contents
Protein chains
258 a.a. *
Ligands
SO4 ×4
GLU ×2
Waters ×581
* Residue conservation analysis
PDB id:
3b6w
Name: Membrane protein
Title: Crystal structure of the glur2 ligand binding core (s1s2j) t686s mutant in complex with glutamate at 1.7 resolution
Structure: Glutamate receptor 2. Chain: a, b, c, d. 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, glur2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.70Å     R-factor:   0.227     R-free:   0.260
Authors: Y.Cho,E.Lolis,J.R.Howe
Key ref: W.Zhang et al. (2008). Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating. J Neurosci, 28, 932-943. PubMed id: 18216201 DOI: 10.1523/JNEUROSCI.3309-07.2008
Date:
29-Oct-07     Release date:   05-Feb-08    
PROCHECK
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 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 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: 10.1523/JNEUROSCI.3309-07.2008 J Neurosci 28:932-943 (2008)
PubMed id: 18216201  
 
 
Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating.
W.Zhang, Y.Cho, E.Lolis, J.R.Howe.
 
  ABSTRACT  
 
At most excitatory central synapses, glutamate is released from presynaptic terminals and binds to postsynaptic AMPA receptors, initiating a series of conformational changes that result in ion channel opening. Efficient transmission at these synapses requires that glutamate binding to AMPA receptors results in rapid and near-synchronous opening of postsynaptic receptor channels. In addition, if the information encoded in the frequency of action potential discharge is to be transmitted faithfully, glutamate must dissociate from the receptor quickly, enabling the synapse to discriminate presynaptic action potentials that are spaced closely in time. The current view is that the efficacy of agonists is directly related to the extent to which ligand binding results in closure of the binding domain. For glutamate to dissociate from the receptor, however, the binding domain must open. Previously, we showed that mutations in glutamate receptor subunit 2 that should destabilize the closed conformation not only sped deactivation but also altered the relative efficacy of glutamate and quisqualate. Here we present x-ray crystallographic and single-channel data that support the conclusions that binding domain closing necessarily precedes channel opening and that the kinetics of conformational changes at the level of the binding domain importantly influence ion channel gating. Our findings suggest that the stability of the closed-cleft conformation has been tuned during evolution so that glutamate dissociates from the receptor as rapidly as possible but remains an efficacious agonist.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
21297640 C.F.Landes, A.Rambhadran, J.N.Taylor, F.Salatan, and V.Jayaraman (2011).
Structural landscape of isolated agonist-binding domains from single AMPA receptors.
  Nat Chem Biol, 7, 168-173.  
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.  
21372852 M.L.Mayer (2011).
Glutamate receptor ion channels: where do all the calories go?
  Nat Struct Mol Biol, 18, 253-254.  
20107073 A.Birdsey-Benson, A.Gill, L.P.Henderson, and D.R.Madden (2010).
Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors.
  J Neurosci, 30, 1463-1470.
PDB codes: 3kei 3kfm
20335481 M.L.Prieto, and L.P.Wollmuth (2010).
Gating modes in AMPA receptors.
  J Neurosci, 30, 4449-4459.  
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
19648915 C.L.Kussius, and G.K.Popescu (2009).
Kinetic basis of partial agonism at NMDA receptors.
  Nat Neurosci, 12, 1114-1120.  
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.  
18514334 A.D.Milstein, and R.A.Nicoll (2008).
Regulation of AMPA receptor gating and pharmacology by TARP auxiliary subunits.
  Trends Pharmacol Sci, 29, 333-339.  
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
18795801 A.S.Maltsev, A.H.Ahmed, M.K.Fenwick, D.E.Jane, and R.E.Oswald (2008).
Mechanism of partial agonism at the GluR2 AMPA receptor: Measurements of lobe orientation in solution.
  Biochemistry, 47, 10600-10610.  
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
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.