2csa
From Proteopedia
Structure of the M3 Muscarinic Acetylcholine Receptor Basolateral Sorting Signal
Structural highlights
Disease[ACM3_HUMAN] Defects in CHRM3 are the cause of Eagle-Barrett syndrome (EGBRS) [MIM:100100]. EGBRS is a syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities.[1] Function[ACM3_HUMAN] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. Publication Abstract from PubMedMuscarinic 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(275)-Val(281), in the third intracellular loop of the M(3) muscarinic receptor that mediates dominant, position-independent basolateral targeting in Madin-Darby canine kidney cells. Mutational analyses identify Glu(276), Phe(280), and Val(281) as critical residues within this sorting motif. Phe(280) and Val(281) comprise a novel dihydrophobic sorting signal as mutations of either residue singly or together with leucine do not disrupt basolateral targeting. Conversely, Glu(276) is required and cannot be substituted with alanine or aspartic acid. A 19-amino acid peptide representing the M(3) sorting signal and surrounding sequence was analyzed via two-dimensional nuclear magnetic resonance spectroscopy. Solution structures show that Glu(276) resides in a type IV beta-turn and the dihydrophobic sequence Phe(280)Val(281) adopts either a type I or IV beta-turn. Identification and structural determination of the M(3) muscarinic acetylcholine receptor basolateral sorting signal.,Iverson HA, Fox D 3rd, Nadler LS, Klevit RE, Nathanson NM J Biol Chem. 2005 Jul 1;280(26):24568-75. Epub 2005 May 2. PMID:15870063[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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