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PDBsum entry 3c35
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protein ligands metals Protein-protein interface(s) links
Membrane protein PDB id
3c35

 

 

 

 

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Contents
Protein chains
254 a.a. *
Ligands
KAI ×2
GOL ×3
Metals
_CS ×13
_CL
Waters ×400
* Residue conservation analysis
PDB id:
3c35
Name: Membrane protein
Title: Crystal structure of glur5 ligand-binding core in complex with cesium at 1.97 angstrom resolution
Structure: Glutamate receptor, ionotropic kainate 1. Chain: a, b. Fragment: residues 446-821. Synonym: glutamate receptor 5, glur-5, glur5. Engineered: yes
Source: Rattus norvegicus. Rat. Gene: grik1, glur5. Expressed in: escherichia coli.
Resolution:
1.97Å     R-factor:   0.182     R-free:   0.227
Authors: M.L.Mayer
Key ref: A.J.Plested et al. (2008). Molecular basis of kainate receptor modulation by sodium. Neuron, 58, 720-735. PubMed id: 18549784
Date:
27-Jan-08     Release date:   17-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P22756  (GRIK1_RAT) -  Glutamate receptor ionotropic, kainate 1 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		949 a.a.
254 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
Neuron 58:720-735 (2008)
PubMed id: 18549784  
 
 
Molecular basis of kainate receptor modulation by sodium.
A.J.Plested, R.Vijayan, P.C.Biggin, M.L.Mayer.
 
  ABSTRACT  
 
Membrane proteins function in a polarized ionic environment with sodium-rich extracellular and potassium-rich intracellular solutions. Glutamate receptors that mediate excitatory synaptic transmission in the brain show unusual sensitivity to external ions, resulting in an apparent requirement for sodium in order for glutamate to activate kainate receptors. Here, we solve the structure of the Na(+)-binding sites and determine the mechanism by which allosteric anions and cations regulate ligand-binding dimer stability, and hence the rate of desensitization and receptor availability for gating by glutamate. We establish a stoichiometry for binding of 2 Na(+) to 1 Cl(-) and show that allosteric anions and cations bind at physically discrete sites with strong electric fields, that the binding sites are not saturated in CSF, and that the requirement of kainate receptors for Na(+) occurs simply because other cations bind with lower affinity and have lower efficacy compared to Na(+).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21349697 M.L.Mayer (2011).
Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.
  Curr Opin Neurobiol, 21, 283-290.  
20199107 A.H.Ahmed, C.P.Ptak, and R.E.Oswald (2010).
Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA.
  Biochemistry, 49, 2843-2850.
PDB codes: 3m3f 3m3k 3m3l
20850188 D.Perrais, J.Veran, and C.Mulle (2010).
Gating and permeation of kainate receptors: differences unveiled.
  Trends Pharmacol Sci, 31, 516-522.  
  20066666 H.Ogawa, Y.Qiu, J.S.Philo, T.Arakawa, C.M.Ogata, and K.S.Misono (2010).
Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: possible allosteric regulation and a conserved structural motif for the chloride-binding site.
  Protein Sci, 19, 544-557.
PDB code: 3a3k
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.  
18687343 A.J.Plested, and M.L.Mayer (2009).
Engineering a high-affinity allosteric binding site for divalent cations in kainate receptors.
  Neuropharmacology, 56, 114-120.  
19946269 A.N.Thompson, I.Kim, T.D.Panosian, T.M.Iverson, T.W.Allen, and C.M.Nimigean (2009).
Mechanism of potassium-channel selectivity revealed by Na(+) and Li(+) binding sites within the KcsA pore.
  Nat Struct Mol Biol, 16, 1317-1324.
PDB codes: 3gb7 3iga
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
19910922 E.Karakas, N.Simorowski, and H.Furukawa (2009).
Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit.
  EMBO J, 28, 3910-3920.
PDB codes: 3jpw 3jpy
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.  
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.  
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.  
19254535 R.Vijayan, A.J.Plested, M.L.Mayer, and P.C.Biggin (2009).
Selectivity and cooperativity of modulatory ions in a neurotransmitter receptor.
  Biophys J, 96, 1751-1760.  
18592294 J.P.Reyes, P.Pérez-Cornejo, C.Y.Hernández-Carballo, A.Srivastava, V.G.Romanenko, M.Gonzalez-Begne, J.E.Melvin, and J.Arreola (2008).
Na+ modulates anion permeation and block of P2X7 receptors from mouse parotid glands.
  J Membr Biol, 223, 73-85.  
18987182 S.J.Pitt, L.G.Sivilotti, and M.Beato (2008).
High intracellular chloride slows the decay of glycinergic currents.
  J Neurosci, 28, 11454-11467.  
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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