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A number of peripheral membrane proteins functioning as regulatory enzymes are distributed between soluble and particulate fractions upon homogenization and subcellular fractionation. One such enzyme, the Ca2+/phospholipid-dependent protein kinase, protein kinase C, was analyzed in order to examine this characteristic of differential localization. The soluble and particulate forms of this enzyme were purified to relative homogeneity, and their biochemical and biophysical properties were analyzed and compared. Based on biochemical activities, the particulate form required lower phospholipid concentrations for maximal activation than for the soluble species. The particulate species had a more hydrophobic structure as demonstrated by a hydrophobic fluorescence probe, and had almost 50% more -helical structures according to secondary structure estimation, determined from far ultra-violet-circular dichroism spectra (200–250 nm). Using Fourier transform infrared spectroscopy, specific lipid spectra were detected associated with the soluble protein kinase C species. Further analyses with a fluorescent neutral membrane probe suggested that there was more lipid associated with the purified particulate form, which was of a less mobile nature than those associated with the soluble species. These structural differences provide an explanation for the preferential localization of the enzyme and may prove to be the basis for distribution of other membrane-active peripheral membrane regulatory enzymes. 相似文献
55.
Electrical sizing of particles in suspensions. II. Experiments with rigid spheres 总被引:6,自引:2,他引:4
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Experimental verification is provided for the theoretical expressions (see preceding article, I. Theory) describing the electrical processes that take place during the passage of an aqueous suspension of rigid, nonconducting spheres (ragweed pollen) through an orifice across which there exists an electrical field, for a large range of orifice dimensions; the instrumentation developed is considered in some detail. The effective length of an orifice as deduced from conductivity measurements is shown to be essentially the same as that predicted theoretically. Absolute volume distributions are presented of a suspension of polystyrene latex spheres as determined electrically (mean 11.17 μ3, c. v. 4.2%) and with an electron microscope (mean 11.01 μ3, c. v. 4.1%). Conflicting experimental results reported in the literature are discussed. 相似文献
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Nadav Y. Denekamp Koushirou Suga Atsushi Hagiwara Richard Reinhardt Esther Lubzens 《Hydrobiologia》1989,(1):XVII
Pater Dr.h.c. Josef Donner (28.2.1909–8.1.1989) in memoriam 相似文献
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The p38 mitogen-activated protein kinases are activated in response to various extracellular signals in eukaryotic cells and play a critical role in the cellular responses to these signals. The four mammalian isoforms (p38alpha, p38beta, p38gamma, and p38delta) are coexpressed and coactivated in the same cells. The exact role of each p38 isoform has not been entirely identified, in part due to the inability to activate each member individually. This could be resolved by the use of intrinsically active mutants. Based on previous studies on yeast p38/Hog1 [Bell M, Capone R, Pashtan I, Levitzki A & Engelberg D (2001) J Biol Chem276, 25351-2538] and human p38alpha[Diskin R, Askari N, Capone R, Engelberg D & Livnah O (2004) J Biol Chem279, 47040-47049] we have generated intrinsically active p38beta, p38gamma and p38delta mutants. In addition, we have identified a new activating mutation site in p38alpha. Most of the activating mutations are located in the L16 loop, in which conformational changes were shown to induce activation. We show that these changes impose substantial autophosphorylation activity, providing a mechanistic explanation for the intrinsic activity of the mutants. The new active variants maintain specificity towards substrates and inhibitors similar to that of the parental wild-type proteins, and are phosphorylated by mitogen-activated protein kinase kinase 6, their upstream activator. Thus, we have completed the development of a series of intrinsically active mutants of all p38 isoforms. These active variants could now become powerful tools for the elucidating the activation mechanism and specific biological roles of each p38 isoform. 相似文献
59.
Evolutionary conservation of sequence and secondary structures in CRISPR repeats 总被引:3,自引:0,他引:3
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Background
Clustered regularly interspaced short palindromic repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in approximately 40% of bacterial and most archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CASs), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been recently shown that CRISPR provides acquired resistance against viruses in prokaryotes. 相似文献60.
NOD1 (NLRC1) is a member of the NLR family of innate immunity proteins, which are important cellular sensors of various pathogens. Deregulated NOD1 signaling is involved in various autoimmune, inflammatory, and allergic diseases, making it a potential target for drug discovery. However, to date, the successful high-yield purification NOD1 protein has not been reported. Here we describe the large-scale expression of recombinant NOD1 protein in non-adherent mammalian cells. One-step immunoaffinity purification was carried out, yielding highly pure protein with excellent yields. Gel-sieve chromatography studies showed that the purified NOD1 protein eluted almost exclusively as a monomer. Addition of the NOD1 ligand (γ-Tri-DAP) stimulated NOD1 protein oligomerization. Using purified NOD1 protein for nucleotide binding studies by the Fluorescence Polarization Assay (FPA) method, we determined that NOD1 binds preferentially to ATP over ADP and AMP or dATP. We also documented that purified NOD1 protein binds directly to purified pro-apoptotic protein Bid, thus extending recent data that have identified Bid as an enhancer of NOD1 signaling. This expression and purification strategy will enable a wide variety of biochemical studies of mechanisms of NOD1 regulation, as well as laying a foundation for future attempts at drug discovery. 相似文献