Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation.

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Changeux, JP; Christopoulos, A
Year of Publication: 2016
Journal: Cell
Volume: 166
Number: 5
Pagination: 1084-102
Date Published: Aug 25
Publication Language: eng
ISBN Number: 0092-8674
Accession Number: 27565340
Abstract:

Four major receptor families enable cells to respond to chemical and physical signals from their proximal environment. The ligand- and voltage-gated ion channels, G-protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases are all allosteric proteins that carry multiple, spatially distinct, yet conformationally linked ligand-binding sites. Recent studies point to common mechanisms governing the allosteric transitions of these receptors, including the impact of oligomerization, pre-existing and functionally distinct conformational ensembles, intrinsically disordered regions, and the occurrence of allosteric modulatory sites. Importantly, synthetic allosteric modulators are being discovered for these receptors, providing an enriched, yet challenging, landscape for novel therapeutics.

Author Address:

Collège de France and CNRS URA 2182, Institut Pasteur, 75015 Paris, France. Electronic address: changeux@noos.fr. Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052 Parkville, Australia. Electronic address: arthur.christopoulos@monash.edu.

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