Identification and Structural Determination of the M sub(3) Muscarinic Acetylcholine Receptor Basolateral Sorting Signal
Muscarinic acetylcholine receptors comprise a family of G-protein-coupled receptors that display differential localization in polarized epithelial cells. We identify a seven-residue sequence, Ala super(275)-Val super(281), in the third intracellular loop of the M sub(3) muscarinic receptor that medi...
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Published in | The Journal of biological chemistry Vol. 280; no. 26; pp. 24568 - 24575 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.07.2005
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Online Access | Get full text |
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Summary: | Muscarinic acetylcholine receptors comprise a family of G-protein-coupled receptors that display differential localization in polarized epithelial cells. We identify a seven-residue sequence, Ala super(275)-Val super(281), in the third intracellular loop of the M sub(3) muscarinic receptor that mediates dominant, position-independent basolateral targeting in Madin-Darby canine kidney cells. Mutational analyses identify Glu super(276), Phe super(280), and Val super(281) as critical residues within this sorting motif. Phe super(280) and Val super(281) comprise a novel dihydrophobic sorting signal as mutations of either residue singly or together with leucine do not disrupt basolateral targeting. Conversely, Glu super(276) is required and cannot be substituted with alanine or aspartic acid. A 19-amino acid peptide representing the M sub(3) sorting signal and surrounding sequence was analyzed via two-dimensional nuclear magnetic resonance spectroscopy. Solution structures show that Glu super(276) resides in a type IV beta -turn and the dihydrophobic sequence Phe super(280)Val super(281) adopts either a type I or IV beta -turn. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 0021-9258 1083-351X |