4OR2: Human class C G protein-coupled metabotropic glutamate receptor 1 in complex with a negative allosteric modulator

Citation:
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.
PDB ID: 4OR2Download
MMDB ID: 118496
PDB Deposition Date: 2014/2/10
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4OR2: trimeric; determined by author and by software (PISA)
Molecular Components in 4OR2
Label Count Molecule
Proteins (3 molecules)
3
Soluble Cytochrome B562, Metabotropic Glutamate Receptor 1(Gene symbol: GRM1)
Molecule annotation
Chemicals (19 molecules)
1
3
2
7
3
1
4
4
5
4
* Click molecule labels to explore molecular sequence information.

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