4a4m

Crystal structure of the light-activated constitutively active N2C, M257Y,D282C rhodopsin mutant in complex with a peptide resembling the C-terminus of the Galpha-protein subunit (GaCT)

spinqualitylabelsall models 4a4m, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4a4m is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.3Å Ligands: ACE, ACT, BOG, NAG, PLM, RET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OPSD_BOVIN Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal (By similarity). Publication Abstract from PubMed G protein-coupled receptors (GPCR) are seven transmembrane helix proteins that couple binding of extracellular ligands to conformational changes and activation of intracellular G proteins, GPCR kinases, and arrestins. Constitutively active mutants are ubiquitously found among GPCRs and increase the inherent basal activity of the receptor, which often correlates with a pathological outcome. Here, we have used the M257Y(6.40) constitutively active mutant of the photoreceptor rhodopsin in combination with the specific binding of a C-terminal fragment from the G protein alpha subunit (GalphaCT) to trap a light activated state for crystallization. The structure of the M257Y/GalphaCT complex contains the agonist all-trans-retinal covalently bound to the native binding pocket and resembles the G protein binding metarhodopsin-II conformation obtained by the natural activation mechanism; i.e., illumination of the prebound chromophore 11-cis-retinal. The structure further suggests a molecular basis for the constitutive activity of 6.40 substitutions and the strong effect of the introduced tyrosine based on specific interactions with Y223(5.58) in helix 5, Y306(7.53) of the NPxxY motif and R135(3.50) of the E(D)RY motif, highly conserved residues of the G protein binding site. Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II.,Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):119-24. Epub 2011 Dec 23. PMID:22198838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rhodopsin 3D structures

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