PDBsum entry 2v3t

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protein metals Protein-protein interface(s) links
Receptor PDB id
Protein chains
245 a.a. *
255 a.a. *
_CA ×2
Waters ×30
* Residue conservation analysis
PDB id:
Name: Receptor
Title: Structure of the ligand-binding core of the ionotropic glutamate receptor-like glurdelta2 in the apo form
Structure: Glutamate receptor delta-2 subunit synonym glurdelta2, glur delta-2. Chain: a, b. Fragment: ligand-binding core, residues 440-551 and 664-813. Engineered: yes
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.75Å     R-factor:   0.231     R-free:   0.286
Authors: P.Naur,B.Vestergaard,M.Gajhede,J.S.Kastrup
Key ref:
P.Naur et al. (2007). Ionotropic glutamate-like receptor delta2 binds D-serine and glycine. Proc Natl Acad Sci U S A, 104, 14116-14121. PubMed id: 17715062 DOI: 10.1073/pnas.0703718104
22-Jun-07     Release date:   07-Aug-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q63226  (GRID2_RAT) -  Glutamate receptor ionotropic, delta-2
1007 a.a.
245 a.a.
Protein chain
Pfam   ArchSchema ?
Q63226  (GRID2_RAT) -  Glutamate receptor ionotropic, delta-2
1007 a.a.
255 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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: 10.1073/pnas.0703718104 Proc Natl Acad Sci U S A 104:14116-14121 (2007)
PubMed id: 17715062  
Ionotropic glutamate-like receptor delta2 binds D-serine and glycine.
P.Naur, K.B.Hansen, A.S.Kristensen, S.M.Dravid, D.S.Pickering, L.Olsen, B.Vestergaard, J.Egebjerg, M.Gajhede, S.F.Traynelis, J.S.Kastrup.
The orphan glutamate-like receptor GluRdelta2 is predominantly expressed in Purkinje cells of the central nervous system. The classification of GluRdelta2 to the ionotropic glutamate receptor family is based on sequence similarities, because GluRdelta2 does not form functional homomeric glutamate-gated ion channels in transfected cells. Studies in GluRdelta2(-/-) knockout mice as well as in mice with naturally occurring mutations in the GluRdelta2 gene have demonstrated an essential role of GluRdelta2 in cerebellar long-term depression, motor learning, motor coordination, and synaptogenesis. However, the lack of a known agonist has hampered investigations on the function of GluRdelta2. In this study, the ligand-binding core of GluRdelta2 (GluRdelta2-S1S2) was found to bind neutral amino acids such as D-serine and glycine, as demonstrated by isothermal titration calorimetry. Direct evidence for binding of D-serine and structural rearrangements in the binding cleft of GluRdelta2-S1S2 is provided by x-ray structures of GluRdelta2-S1S2 in its apo form and in complex with D-serine. Functionally, D-serine and glycine were shown to inactivate spontaneous ion-channel conductance in GluRdelta2 containing the lurcher mutation (EC(50) values, 182 and 507 microM, respectively). These data demonstrate that the GluRdelta2 ligand-binding core is capable of binding ligands and that cleft closure of the ligand-binding core can induce conformational changes that alter ion permeation.
  Selected figure(s)  
Figure 1.
Fig. 1. The structure of the ligand-binding core of GluR 2. (A) Domain organization of the GluR 2 receptor subunit. The architecture is similar to other glutamate receptors (AMPA, kainate, and NMDA receptors), with an extracellular N terminus, three transmembrane segments (M1, M2, and M3), a reentrant membrane loop (P), and an intracellular C terminus. The extracellular regions harbor the N-terminal domain (NTD) and the ligand-binding core (D1 and D2). The red dot shows the approximate position of the lurcher mutation (A654T). The boundaries of the GluR 2–S1S2 construct are indicated by scissors, and the dotted line represents the Gly–Thr linker. (B) Representation of the twofold symmetric dimer of GluR 2–S1S2 apo (in yellow). The structure of GluR 2–S1S2 in complex with D-serine has been superimposed onto GluR 2–S1S2 apo and is shown in red. D-serine is displayed as green spheres.
Figure 3.
Fig. 3. The structure of the ligand-binding core of GluR 2 in complex with D-serine. (A) The D-serine-binding site of GluR 2–S1S2. The F[o] – F[c] electron-density map of D-serine before introduction of this molecule in the refinements is shown. D-serine and potential hydrogen-bonding residues of GluR 2 are represented as sticks, and dashed lines indicate hydrogen bonds. (B) Contour of the ligand-binding cavity of GluR 2–S1S2 in complex with D-serine (shown in gray). D-serine and GluR 2 residues within 3.5 Å are represented as sticks. No water molecules were located within the hydrogen-bonding distance of D-serine.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21342763 M.Yuzaki (2011).
Cbln1 and its family proteins in synapse formation and maintenance.
  Curr Opin Neurobiol, 21, 215-220.  
21460832 W.Kakegawa, Y.Miyoshi, K.Hamase, S.Matsuda, K.Matsuda, K.Kohda, K.Emi, J.Motohashi, R.Konno, K.Zaitsu, and M.Yuzaki (2011).
D-serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor.
  Nat Neurosci, 14, 603-611.  
21080238 T.Nakagawa (2010).
The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors.
  Mol Neurobiol, 42, 161-184.  
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.  
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.  
  19184587 G.T.Swanson, and R.Sakai (2009).
Ligands for ionotropic glutamate receptors.
  Prog Mol Subcell Biol, 46, 123-157.  
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
  20054121 M.Fiorentini, A.K.Nielsen, O.Kristensen, J.S.Kastrup, and M.Gajhede (2009).
Structure of the first PDZ domain of human PSD-93.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1254-1257.
PDB code: 2wl7
19135896 R.Benton, K.S.Vannice, C.Gomez-Diaz, and L.B.Vosshall (2009).
Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila.
  Cell, 136, 149-162.  
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.  
19258455 T.Kuroyanagi, M.Yokoyama, and T.Hirano (2009).
Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.
  Proc Natl Acad Sci U S A, 106, 4912-4916.  
19614753 T.Torashima, A.Iizuka, H.Horiuchi, K.Mitsumura, M.Yamasaki, C.Koyama, K.Takayama, M.Iino, M.Watanabe, and H.Hirai (2009).
Rescue of abnormal phenotypes in delta2 glutamate receptor-deficient mice by the extracellular N-terminal and intracellular C-terminal domains of the delta2 glutamate receptor.
  Eur J Neurosci, 30, 355-365.  
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
18521762 S.M.Schmid, and M.Hollmann (2008).
To gate or not to gate: are the delta subunits in the glutamate receptor family functional ion channels?
  Mol Neurobiol, 37, 126-141.  
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.