Membrane tethering enables an extracellular domain of the acetylcholine receptor alpha subunit to form a heterodimeric ligand-binding site.
The first step of assembly of the nicotinic acetylcholine receptor (AChR) of adult skeletal muscle is the specific association of the alpha subunit with either delta or epsilon subunits to form a heterodimer with a ligand-binding site. Previous experiments have suggested that het erodimer formation in the ER arises from interaction between the luminal, NH2-terminal domains of the subunits. When expressed in COS cells with the delta subunit, however, the truncated NH2-terminal domain of the subunit folded correctly but did not form a heterodimer. Association with the delta subunit occurred only when the NH2-terminal domain was retained in the ER and was tethered to the membrane by its own M1 transmembrane domain, by the transmembrane domain of another protein, or by a glycolipid link. In each case, the ligand-binding sites of the resulting heterodimers were indistinguishable from that formed when the full-length alpha subunit was used. Attachment to the membrane may promote interaction by concentrating or orienting the subunit; alternatively, a membrane-bound factor may facilitate subunit association.
Department of Physiology, University of California School of Medicine, San Francisco 94143, USA.
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Wang
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020126:Brefeldin A; D002038:Bungarotoxins / Q000378:metabolism; D019556:COS Cells; D003517:Cyclopentanes / Q000494:pharmacology; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000737:chemistry; D017261:Glycosylphosphatidylinositols / Q000032:analysis; D007425:Intracellular Membranes / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism
D002038:Bungarotoxins; D003517:Cyclopentanes; D017261:Glycosylphosphatidylinositols; D008024:Ligands; D010446:Peptide Fragments; D011500:Protein Synthesis Inhibitors; D011978:Receptors, Nicotinic; D020126:Brefeldin A