PDBsum entry 2e4u

Signaling protein

PDB id: 2e4u

Contents

Protein chains

512 a.a. *

Ligands

NAG ×2

GLU ×2

Waters ×274

* Residue conservation analysis

PDB id:

2e4u

Name:

Signaling protein

Title:

Crystal structure of the extracellular region of the group ii metabotropic glutamate receptor complexed with l-glutamate

Structure:

Metabotropic glutamate receptor 3. Chain: a, b. Fragment: extracellular region. Synonym: mglur3, group ii metabotropic glutamate receptor subtype 3. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.

Resolution:

2.35Å R-factor: 0.238 R-free: 0.267

Authors:

T.Muto,D.Tsuchiya,K.Morikawa,H.Jingami

Key ref:

T.Muto et al. (2007). Structures of the extracellular regions of the group II/III metabotropic glutamate receptors. Proc Natl Acad Sci U S A, 104, 3759-3764. PubMed id: 17360426 DOI: 10.1073/pnas.0611577104

Date:

17-Dec-06 Release date: 27-Feb-07

Protein chains

P31422  (GRM3_RAT) -  Metabotropic glutamate receptor 3 from Rattus norvegicus

Seq: 879 a.a.

Struc: 512 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1073/pnas.0611577104

Proc Natl Acad Sci U S A 104:3759-3764 (2007)

PubMed id: 17360426

Structures of the extracellular regions of the group II/III metabotropic glutamate receptors.

T.Muto, D.Tsuchiya, K.Morikawa, H.Jingami.

ABSTRACT

Metabotropic glutamate receptors play major roles in the activation of excitatory synapses in the central nerve system. We determined the crystal structure of the entire extracellular region of the group II receptor and that of the ligand-binding region of the group III receptor. A comparison among groups I, II, and III provides the structural basis that could account for the discrimination of group-specific agonists. Furthermore, the structure of group II includes the cysteine-rich domain, which is tightly linked to the ligand-binding domain by a disulfide bridge, suggesting a potential role in transmitting a ligand-induced conformational change into the downstream transmembrane region. The structure also reveals the lateral interaction between the two cysteine-rich domains, which could stimulate clustering of the dimeric receptors on the cell surface. We propose a general activation mechanism of the dimeric receptor coupled with both ligand-binding and interprotomer rearrangements.

Selected figure(s)

Figure 3.
Fig. 3. Agonist recognition by mGluR-II[3]. Schematic drawings for the binding of Glu (A), DCG-IV (B), 1S,3S-ACPD (C), 1S,3R-ACPD (D), and 2R,4R-APDC (E). Hydrogen atoms attached at the C[ ]atom of the ligands are modeled with the corresponding ideal geometries. Only the residues/water molecules that directly interact with one of the agonists are drawn. Red and blue lines indicate hydrogen-bonding and VDW contact, respectively. Either of the two carboxyl oxygen atoms connected by the green line in B is likely to be protonated, as suggested from the short distance between them (2.4 Å).

Figure 4.
Fig. 4. The ligand-binding pocket. (A) Conserved amino acid residues involved in ligand binding. Red, green, and blue stick models represent the structures for mGluR-I[1], mGluR-II[3], and mGluR-III[7], respectively. The three closed protomers were superimposed by least-square fitting. The model of the closed mGluR-III[7] was constructed as described in the text. (B) Difference in the open angle of the closed protomer between mGluR-I[1] (purple) and mGluR-II[3] (green). The yellow stick model represents the bound Glu. The black arrow indicates the view direction in A. (C–E) The ligand-binding pockets of mGluR-I[1] (C), mGluR-II[3] (D), and mGluR-III[7] (E) as viewed in A. Each molecular model is colored as in Fig. 1B. Red lines indicate the conserved surface shown in A. (F) Diagram representing the DCG-IV binding of mGluR-II[3], viewed from directions similar to that in A. The structure of the closed protomers of mGluR-I[1] (green) (4) is superimposed onto the mGluR-II[3]structures (yellow).

Figures were selected by an automated process.