Locating GABA in GABA receptor binding sites.
The Cys-loop family of ligand-gated ion channels contains both vertebrate and invertebrate members that are activated by GABA (gamma-aminobutyric acid). Many of the residues that are critical for ligand binding have been identified in vertebrate GABA(A) and GABA(C) receptors, and specific interactions between GABA and some of these residues have been determined. In the present paper, I show how a cation-pi interaction for one of the binding site residues has allowed the production of models of GABA docked into the binding site, and these orientations are supported by mutagenesis and functional data. Surprisingly, however, the residue that forms the cation-pi interaction is not conserved, suggesting that GABA occupies subtly different locations even in such closely related receptors.
Lummis
Sarah C R
SC
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. sl120@cam.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002412:Cations / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D018079:Receptors, GABA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002412:Cations; D018079:Receptors, GABA; D012701:Serotonin; D005680:gamma-Aminobutyric Acid