1Cell surface receptorsFigure 19-23 Domain organization in a variety of receptor tyrosine kinase (RTK) subfamilies.EGF endothelial growth factor; IGF insulin like growth factor; FGF fibroblast growth factor; PDGF Platelet-derived growth factorVoet and Voet, Biochemistry, chapter 192Figure 19-25 Schematic diagrams of RTKs.Extra and intracellular domains are shown disproportionallyVoet and Voet, Biochemistry, chapter 19PDGFreceptorEGFreceptorExtracellular Receptor siteTransmembrane helixCytoplasmic domainTyrosine kinaseDimerizationActivationKinaseLigand bindingTyr-phosphateTyrFig. Transmembrane topology and tyrosine kinase activation mechanism of growth factor receptors Tyrosine Kinase Receptor activation and control by dimerization3Akihiko Ishijima and Toshio Yanagida, Single molecule nanobioscience, TRENDS in Biochemical Sciences Vol.26 No.7 July 2001Tyrosine Kinase Receptor activation and control by dimerizationFigure 19-14 General structure of a G protein-coupled receptor (GPCR).M = Muscarinic acetylcholine receptor4Palczewski et al., 2000, Science 289:739-745.Crystal structure of bovine rhodopsin at 2.8 Å resolutionTop viewIn Top viewOut In Out Domain ‘tinkering’ produces ligand binding and signal transduction pathway diversityJ.Bockaert and J.Ph. Pin, 1999, EMBO J. 18:1723-17295H.R. Petty, Molecular Biology of Membranes, 1993, Plenum Press, NYβ-adrenergic receptor’s ligand binding siteFig. 13-22, Nelson, Cox; Lehninger Principles in Biochemistry, 3rd, Worth Pub., 2001Composite structure of rhodopsin with G-protein transducinG-protein lipid anchorsα subunit: (fatty acids)C14 myristoylation (MGxxxS N-terminal end)C16 palmitoylation (Cys3,9,10 N-terminal end)γ subunit: (isoprenes)C15 farnesylationC20 Geranylgeranylationα subunit palmitoylation is reversible and may allow regulation of available membrane bound subunit.6Voet and Voet, Biochemistry, chapter 22Figure 12-25a Structure of bacteriorhodopsin. (left) The electron crystallography–based structure. Structure of bovine rhodopsinFigure 22-34Proton pump of bacteriorhodopsin.Voet and Voet, Biochemistry, chapter 227Functional studies: Light driven ATP synthesisFlux assay that couples light driven proton flux into a liposome (lipid vesicle) with proton driven ATP
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