2ycy

TURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND ANTAGONIST CYANOPINDOLOL

spinqualitylabelsall models 2ycy, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ycy is a 2 chain structure with sequence from Melga. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA, P32, SOG Related: 1dep, 2y01, 2ycx, 2vt4, 2y04, 2y00, 2y03, 2y02, 2ycw, 2ycz Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ADRB1_MELGA] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Publication Abstract from PubMed The beta(1)-adrenergic receptor (beta(1)AR) is a G-protein-coupled receptor whose inactive state structure was determined using a thermostabilized mutant (beta(1)AR-M23). However, it was not thought to be in a fully inactivated state because there was no salt bridge between Arg139 and Glu285 linking the cytoplasmic ends of transmembrane helices 3 and 6 (the R(3.50) - D/E(6.30) "ionic lock"). Here we compare eight new structures of beta(1)AR-M23, determined from crystallographically independent molecules in four different crystals with three different antagonists bound. These structures are all in the inactive R state and show clear electron density for cytoplasmic loop 3 linking transmembrane helices 5 and 6 that had not been seen previously. Despite significantly different crystal packing interactions, there are only two distinct conformations of the cytoplasmic end of helix 6, bent and straight. In the bent conformation, the Arg139-Glu285 salt bridge is present, as in the crystal structure of dark-state rhodopsin. The straight conformation, observed in previously solved structures of beta-receptors, results in the ends of helices 3 and 6 being too far apart for the ionic lock to form. In the bent conformation, the R(3.50) - E(6.30) distance is significantly longer than in rhodopsin, suggesting that the interaction is also weaker, which could explain the high basal activity in beta(1)AR compared to rhodopsin. Many mutations that increase the constitutive activity of G-protein-coupled receptors are found in the bent region at the cytoplasmic end of helix 6, supporting the idea that this region plays an important role in receptor activation. Two distinct conformations of helix 6 observed in antagonist-bound structures of a {beta}1-adrenergic receptor.,Moukhametzianov R, Warne T, Edwards PC, Serrano-Vega MJ, Leslie AG, Tate CG, Schertler GF Proc Natl Acad Sci U S A. 2011 May 17;108(20):8228-32. Epub 2011 May 3. PMID:21540331 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures

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