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The Journal of Neuroscience, June 15, 1999, 19(12):4847-4854
Mapping the Agonist Binding Site of the GABAA Receptor: Evidence for a
-Strand
Andrew J. Boileau, Amy R. Evers, Anson F. Davis, and Cynthia Czajkowski Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706
GABAA receptors, along with the receptors for acetylcholine, glycine, and serotonin, are members of a ligand-gated ion channel superfamily (Ortells and Lunt, 1995). Because of the paucity of crystallographic information for these ligand-gated channels, little is known about the structure of their binding sites or how agonist binding is transduced into channel gating. We used the substituted cysteine accessibility method to obtain secondary structural information about the GABA binding site and to systematically identify residues that line its surface. Each residue from
1 Y59 to K70 was mutated to cysteine and expressed with wild-type
2 subunits in Xenopus oocytes or HEK 293 cells. The sulfhydryl-specific reagent N-biotinylaminoethyl methanethiosulfonate (MTSEA-Biotin) was used to covalently modify the cysteine-substituted residues. Receptors with cysteines substituted at positions
Key words: GABA; GABAA receptor; binding site; substituted cysteine accessibility method;
Copyright © 1999 Society for Neuroscience 0270-6474/99/19124847-08$05.00/0
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