PDBsum entry 2v3u

Receptor

PDB id: 2v3u

Contents

Protein chain

253 a.a. *

Ligands

DSN

SCN ×2

Metals

_NA

_CL

Waters ×135

* Residue conservation analysis

PDB id:

2v3u

Name:

Receptor

Title:

Structure of the ligand-binding core of the ionotropic glutamate receptor-like glurdelta2 in complex with d-serine

Structure:

Glutamate receptor delta-2 subunit. Chain: a. Fragment: ligand-binding core, residues 440-551,664-813. Synonym: glurdelta2, glur delta-2. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.74Å R-factor: 0.200 R-free: 0.250

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

Date:

22-Jun-07 Release date: 07-Aug-07

Protein chain

Q63226  (GRID2_RAT) -  Glutamate receptor ionotropic, delta-2 from Rattus norvegicus

Seq: 1007 a.a.

Struc: 253 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

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.

ABSTRACT

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.