2csa

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2csa

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Structure of the M3 Muscarinic Acetylcholine Receptor Basolateral Sorting Signal

Overview

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(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.

About this Structure

2CSA is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

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

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