STRUCTURAL BIOLOGY OF THE GLYCINE RECEPTOR

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DESCRIPTION: The overall goal of this proposal is the structure determination of recombinant human a1 glycine receptor chloride channel. The glycine receptor is part of a large family of ligand-gated channels that mediate signal transduction at the synapse. The structure of one member of this family, the acetylcholine receptor, has been studied in three dimensions by electron microscopy and a low resolution structure is available, however the sequence has not been mapped into this structure. Experiments are aimed at distinguishing plausible topological models for this family of channels by labeling cysteine residues engineered into the glycine receptor with chemical cleavage reagents. A major goal of the proposal is to crystallize purified holoreceptor as well as its extracellular, ligand binding domain. Functional glycine receptor composed of a single subunit type can be reconstituted from recombinant protein, and is produced in the co-P.I's lab in large enough yields for crystallization trials.