4OO9

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

4OO9 の概要

• エントリーDOI: 10.2210/pdb4oo9/pdb
• 分子名称: Metabotropic glutamate receptor 5, Lysozyme, Metabotropic glutamate receptor 5 chimera, OLEIC ACID, Mavoglurant, ... (5 entities in total)
• 機能のキーワード: 7tm, receptor, g-protein, cysteine-s-acetamide, membrane protein
• 由来する生物種: Homo sapiens (human, T4 phage, human); 詳細
• 細胞内の位置: Cell membrane {ECO:0000269|PubMed:7908515, ECO:0000269|Ref: P41594
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51555.11

構造登録者

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. (登録日: 2014-01-31, 公開日: 2014-07-02, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)