PDBsum entry 4or2

Signaling protein

PDB id: 4or2

Contents

Protein chains

360 a.a.

Ligands

FM9 ×2

CLR ×6

OLA

OLC ×3

PO4 ×2

Waters ×13

PDB id:

4or2

Name:

Signaling protein

Title:

Human class c g protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator

Structure:

Soluble cytochrome b562, metabotropic glutamate receptor 1. Chain: a, b. Synonym: cytochrome b-562, mglur1. Engineered: yes. Mutation: yes. Other_details: chimera protein of soluble cytochrome b562 from escherichia coli (p0abe7) and residues 581-860 from metabotropic glutamate receptor 1 from homo sapiens (q13255).

Source:

Escherichia coli, homo sapiens. Human. Organism_taxid: 562, 9606. Gene: cybc, grm1_human, gprc1a, grm1, mglur1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.80Å R-factor: 0.229 R-free: 0.268

Authors:

H.Wu,C.Wang,K.J.Gregory,G.W.Han,H.P.Cho,Y.Xia,C.M.Niswender, V.Katritch,V.Cherezov,P.J.Conn,R.C.Stevens,Gpcr Network (Gpcr)

Key ref:

H.Wu et al. (2014). Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science, 344, 58-64. PubMed id: 24603153 DOI: 10.1126/science.1249489

Date:

10-Feb-14 Release date: 19-Mar-14

Protein chains

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 360 a.a.*

Protein chains

Q13255  (GRM1_HUMAN) -  Metabotropic glutamate receptor 1 from Homo sapiens

Seq: 1194 a.a.

Struc: 360 a.a.*

* PDB and UniProt seqs differ at 101 residue positions (black crosses)

DOI no: 10.1126/science.1249489

Science 344:58-64 (2014)

PubMed id: 24603153

Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.

H.Wu, C.Wang, K.J.Gregory, G.W.Han, H.P.Cho, Y.Xia, C.M.Niswender, V.Katritch, J.Meiler, V.Cherezov, P.J.Conn, R.C.Stevens.

ABSTRACT

The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.