Dynamics and modulation of metabotropic glutamate receptors

• Published in: Current opinion in pharmacology Vol. 20; pp. 95 - 101
• Main Authors: Rondard, Philippe, Pin, Jean-Philippe
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2015; Elsevier
• Subjects: Allosteric Regulation - drug effects; Central Nervous System - metabolism; Drug Design; Glutamic Acid - metabolism; Humans; Internal Medicine; Life Sciences; Ligands; Medical Education; Mental Disorders - drug therapy; Mental Disorders - physiopathology; Molecular Targeted Therapy; Nervous System Diseases - drug therapy; Nervous System Diseases - physiopathology; Receptors, Metabotropic Glutamate - drug effects; Receptors, Metabotropic Glutamate - metabolism; Synaptic Transmission - physiology; Allosteric Regulation/drug effects; Central Nervous System/metabolism; Receptors; Glutamic Acid/metabolism; Metabotropic Glutamate/drug effects/metabolism; Mental Disorders/drug therapy/physiopathology; Humans; Drug Design; Ligands; Nervous System Diseases/drug therapy/physiopathology; Molecular Targeted Therapy; Synaptic Transmission/physiology
• ISSN: 1471-4892; 1471-4973
• DOI: 10.1016/j.coph.2014.12.001

Highlights • ECD dimers oscillate between resting and active states on a sub-millisecond time scale. • Agonists shift the ECD dimers equilibrium towards the activated state. • The mGluR 7TM crystal structures reveal the molecular basis of allosteric modulators. • Major change in the 7TM dimer interface during receptor activation. • Time-resolved FRET sensors are powerful tools to study mGluR activation in cells.