Metabotropic glutamate receptor 5 is a disulfide-linked dimer.
The sequences of the metabotropic glutamate receptors (mGluRs) show little homology with other members of the G protein-coupled receptor family and exhibit several distinctive features, including a large N-terminal extracellular domain with 17 cysteines in conserved positions. Here we demonstrate that mGluR5, as well as other mGluRs, behave as species approximately twice as large as expected from their sequence, but reducing conditions cause a decrease to the predicted molecular mass. Co-immunoprecipitation experiments using wild type and epitope-tagged receptors demonstrate that this is due to specific, disulfide-dependent dimerization of the receptor. The intermolecular disulfide that mediates dimerization occurs in the extracellular domain, within about 17 kDa from the N terminus.
Romano
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Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. romano@am.seer.wustl.edu
Yang
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O'Malley
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D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003545:Cysteine; D004220:Disulfides / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D004220:Disulfides; C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D003545:Cysteine