metabotropic Glutamate Receptor 5 Homo sapiens

Introduction

G-coupled protein receptors GPCR are trans-membrane proteins that are integral to cell signaling. The human genome encodes for approximately 750 GPCRS, 350 of which are known to respond to extracellular ligands.^[1]. GPCRs are divided into four major classes; Class A,B,C, and F.^[2]. Metabotropic Glutamate Receptor 5 (mGlu₅) is a class C GPCR that is involved in the G_q pathway ^[3]. mGlu₅is highly expressed in neuronal and glial cells in the central nervous system, where glutamate serves as the major neurotransmitter. When glutamate binds to the extracellular domain of mGlu₅, consisting of the Venus Fly Trap ^[4], a conformational change through the tram-membrane domains activates the coupled G-protein. This G-protein disassociates and the alpha subunit activates Phospholipase C which has the final outcome of increased neuronal activity^[2].

Amidase

GPCR

Structure

Overall Stucture

mGlu₅ is seen as a homodimer ‘in vivo’, with each subunit comprising three domains; extracellular, trans-membrane and intracellular. The structures shown here are centered on the trans-membrane domain, comprised of seven α-helices all roughly parallel to one another ^[4].

Disease

Clinical Relevance

Hydrophobic Pocket Surrounding Mavoglurant

Further Hydrogen Bonding between protein and Mavoglurant