Function and structure in glycine receptors and some of their relatives.
In the field of ligand-gated ion channels, recent developments, both in the knowledge of structure and in the measurement of function at the single-channel level, have allowed a sensible start to be made on understanding the relationship between structure and function in these proteins. In this review, the cases of glycine, nicotinic ACh and glutamate receptors are compared and contrasted, and problems such as how binding of agonist causes the channel to open, and why partial agonists are partial, are considered. Some observations, both structural and functional, suggest that more attention needs to be paid to conformational changes that occur before the channel opens. Such changes might account for the interaction found between subunits of the glycine receptor while it is still shut and, perhaps, the agonist-dependent structural changes seen in AMPA receptors. They might also complicate our understanding of the binding-gating problem.
Colquhoun
David
D
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. d.colquhoun@ucl.ac.uk
Sivilotti
Lucia G
LG
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D017470:Receptors, Glutamate / Q000737:chemistry / Q000502:physiology; D018009:Receptors, Glycine / Q000737:chemistry* / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology
D007473:Ion Channels; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic