Heterotrimeric guanine nucleotide-binding proteins (G proteins) transmit signals from membrane bound G protein-coupled receptors
(GPCRs) to intracellular effector proteins. The G q subfamily of Gα ...subunits couples GPCR activation to the enzymatic activity of phospholipase C-β (PLC-β). Regulators of G
protein signaling (RGS) proteins bind to activated Gα subunits, including Gα q , and regulate Gα signaling by acting as GTPase activating proteins (GAPs), increasing the rate of the intrinsic GTPase activity,
or by acting as effector antagonists for Gα subunits. GPCR kinases (GRKs) phosphorylate agonist-bound receptors in the first
step of receptor desensitization. The amino termini of all GRKs contain an RGS homology (RH) domain, and binding of the GRK2
RH domain to Gα q attenuates PLC-β activity. The RH domain of GRK2 interacts with Gα q/11 through a novel Gα binding surface termed the âCâ site. Here, molecular modeling of the Gα q ·GRK2 complex and site-directed mutagenesis of Gα q were used to identify residues in Gα q that interact with GRK2. The model identifies Pro 185 in Switch I of Gα q as being at the crux of the interface, and mutation of this residue to lysine disrupts Gα q binding to the GRK2-RH domain. Switch III also appears to play a role in GRK2 binding because the mutations Gα q -V240A, Gα q -D243A, both residues within Switch III, and Gα q -Q152A, a residue that structurally supports Switch III, are defective in binding GRK2. Furthermore, GRK2-mediated inhibition
of Gα q -Q152A-R183C-stimulated inositol phosphate release is reduced in comparison to Gα q -R183C. Interestingly, the model also predicts that residues in the helical domain of Gα q interact with GRK2. In fact, the mutants Gα q -K77A, Gα q -L78D, Gα q -Q81A, and Gα q -R92A have reduced binding to the GRK2-RH domain. Finally, although the mutant Gα q -T187K has greatly reduced binding to RGS2 and RGS4, it has little to no effect on binding to GRK2. Thus the RH domain A and
C sites for Gα q interaction rely on contacts with distinct regions and different Switch I residues in Gα q .
The effect of various Lewis acids on the dimerisation and polymerisation of aromatic substrates has been investigated. In the dimerisation of 1-ethoxynaphthalene, to 4,4'-diethoxy-1,1'-binaphthyl, it ...was found that the catalyst system ferric chloride in nitrobenzene resulted in higher yields than any other catalyst investigated. A variety of novel polymers were prepared by allowing difunctional substrates, containing the 1-naphthyl ether group, to react with ferric chloride in nitrobenzene: diagram. A study has been made of the variation of properties of a homologous series of poly (dinaphthyl alkylene ethers): diagram with the number of methylene groups in the structure Cm). Melting points, melt viscosities and densities decreased, while impact strength increased with m. The "zig-zag" pattern of change of properties with m diminished as m increased. The dimerisation of 1-ethoxynaphthalene has also been studied kinetically. Initial rates of disappearance of 1-ethoxynaphthalene and appearance of ferrous ion were followed, and an initial rate equation derived: initial rate = kO 1-ethoxynaphthaleneO1/2FeCl3O. In experiments with added hydrogen chloride, the initial rate was found to be inversely proportional to the concentration of hydrogen chloride. When either 1-ethoxynaphthalene or its dimer is allowed to react with ferric chloride in nitrobenzene, red or green coloured solutions are formed. As a result of a spectroscopic study of these solutions, it was concluded that three intermediates are involved in the dimerisation, and that the red solutions contain a paramagentic species that can be formed from both substrate and dimer. A reaction mechanism for the dimerisation of 1-ethoxynaphthalene by ferric chloride in nitrobenzene has been put forward; the mechanism involves two charge transfer complexes and a radical cation as intermediate species. However, it has not proved possible to confirm this proposed mechanism through the observed kinetic data.
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