4OO9

Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant

Summary for 4OO9

• Entry DOI: 10.2210/pdb4oo9/pdb
• Descriptor: Metabotropic glutamate receptor 5, Lysozyme, Metabotropic glutamate receptor 5 chimera, OLEIC ACID, Mavoglurant, ... (5 entities in total)
• Functional Keywords: 7tm, receptor, g-protein, cysteine-s-acetamide, membrane protein
• Biological source: Homo sapiens (human, T4 phage, human); More
• Cellular location: Cell membrane {ECO:0000269|PubMed:7908515, ECO:0000269|Ref: P41594
• Total number of polymer chains: 1
• Total formula weight: 51555.11

Authors

Dore, A.S.,Okrasa, K.,Patel, J.C.,Serrano-Vega, M.,Bennett, K.,Cooke, R.M.,Errey, J.C.,Jazayeri, A.,Khan, S.,Tehan, B.,Weir, M.,Wiggin, G.R.,Marshall, F.H. (deposition date: 2014-01-31, release date: 2014-07-02, Last modification date: 2023-09-20)

Primary citation

Dore, A.S.,Okrasa, K.,Patel, J.C.,Serrano-Vega, M.,Bennett, K.,Cooke, R.M.,Errey, J.C.,Jazayeri, A.,Khan, S.,Tehan, B.,Weir, M.,Wiggin, G.R.,Marshall, F.H.
Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain.
Nature, 511:557-562, 2014

PubMed Abstract: Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.

PubMed: 25042998
DOI: 10.1038/nature13396

Experimental method

X-RAY DIFFRACTION (2.6 Å)