Anxiety over GABA(A) receptor structure relieved by AChBP.
The GABA(A) receptor is the primary mediator of inhibitory neurotransmission in the brain and is a major target for neuromodulatory drugs such as benzodiazepines, barbiturates, ethanol and anaesthetics. However, our understanding of the molecular details of this receptor has been limited by a lack of high-resolution structural information. This article presents a new model for the extracellular, ligand-binding domain of the GABA(A) receptor, that is based on the recently determined structure of a soluble acetylcholine-binding protein. The model puts existing mutational and biochemical data into a three-dimensional context, shows details of the GABA- and benzodiazepine-binding sites, and highlights the importance of other regions in allosteric conformational change. This provides a new perspective on existing data and an exciting new framework for understanding this important family of receptors.
Cromer
Brett A
BA
Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. b.cromer@medicine.unimelb.edu.au
Morton
Craig J
CJ
Parker
Michael W
MW
D000495:Allosteric Site; D000595:Amino Acid Sequence; D001569:Benzodiazepines / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*
C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D007473:Ion Channels; D011963:Receptors, GABA-A; D001569:Benzodiazepines