PDBsum entry 3dln

Signaling protein

PDB id: 3dln

Contents

Protein chain

258 a.a. *

Ligands

GLU

Metals

_ZN

Waters ×205

* Residue conservation analysis

PDB id:

3dln

Name:

Signaling protein

Title:

Crystal structure of the binding domain of the ampa subunit glur3 bound to glutamate

Structure:

Glutamate receptor 3. Chain: a. Fragment: s1s2 binding domain. Synonym: glur-3, glur-c, glur-k3, glutamate receptor ionotropic, ampa 3, ampa-selective glutamate receptor 3. Engineered: yes

Source:

Rattus norvegicus. Organism_taxid: 10116. Gene: gria3, glur3. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.91Å R-factor: 0.197 R-free: 0.235

Authors:

A.H.Ahmed,Q.Wang,H.Sondermann,R.E.Oswald

Key ref:

A.H.Ahmed et al. (2008). Structure of the S1S2 glutamate binding domain of GLuR3. Proteins, 75, 628-637. PubMed id: 19003990 DOI: 10.1002/prot.22274

Date:

27-Jun-08 Release date: 25-Nov-08

Protein chain

P19492  (GRIA3_RAT) -  Glutamate receptor 3 from Rattus norvegicus

Seq: 888 a.a.

Struc: 258 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1002/prot.22274

Proteins 75:628-637 (2008)

PubMed id: 19003990

Structure of the S1S2 glutamate binding domain of GLuR3.

A.H.Ahmed, Q.Wang, H.Sondermann, R.E.Oswald.

ABSTRACT

Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X-ray crystallography to 1.9, 2.1, and 1.55 A, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 +/- 0.05 for glutamate-bound and 0.26 +/- 0.01 for AMPA-bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl-HIBO, which has a 10-fold difference in affinity for GluR2 vs. GluR3). Proteins 2009. (c) 2008 Wiley-Liss, Inc.

Selected figure(s)

Figure 3.
Figure 3. (A) The dimeric structure of GluR3 bound to glutamate. The helices are labeled as in Armstrong et al.[6] Residues participating in contacts across the dimer interface are labeled. P632 (yellow) flanks the artificial linker region of the construct and is the point that connects to the linkers to the ion channel. The four residues that differ in flip and flop are shown in shades of red. (B) The dimer interface at the S754 (flip)/N754 (flop) interaction with S729. Both can form hydrogen bonds, but the structure of the water surrounding the hydrogen bond differs.

Figure 4.
Figure 4. (A) Binding of [^3H]AMPA to the S1S2 domains of GluR2[o] and GluR3[i]. The K[D] of binding differed by less than twofold: 19 ± 2 nM for GluR2 and 43 ± 5 nM for GluR3. Armstrong and Gouaux[5] reported a K[D] of 24.8 ± 1.8 nM for [^3H]AMPA binding to GluR2. (B) Structures of the ligands used in the binding studies, (C) The inhibition of [^3H]AMPA binding by agonists, partial agonists, and antagonist to the S1S2 domains of GluR2[o] and GluR3[i]. Except for willardiine, the IC[50] values were within twofold for the two subtypes: (ligand, GluR2 IC[50]/GluR3 IC[50]; IC[50] expressed in M) fluorowillardiine, 0.0040 ± 0009/0.0062 ± 0.0014; iodowillardiine, 0.46 ± 0.05/0.79 ± 0.14; Cl-HIBO, 5.0 ± 0.3/55 ± 4; willardiine, 3.1 ± 0.2/0.99 ± 0.18; UBP277, 135 ± 12/69 ± 10. In all cases, GluR2[o] is shown with filled symbols, and GluR3[i] is shown with open symbols.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 75, 628-637) copyright 2008.

Figures were selected by an automated process.