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81.
Hata S Koyama S Kawahara H Doi N Maeda T Toyama-Sorimachi N Abe K Suzuki K Sorimachi H 《The Journal of biological chemistry》2006,281(16):11214-11224
Calpain is a Ca2+-regulated cytosolic protease. Mammals have 14 calpain genes, half of which are predominantly expressed in specific organ(s); the rest are expressed ubiquitously. A defect in calpains causes lethality/pathogenicity, indicating their physiological indispensability. nCL-2/calpain-8a was identified as a stomach-specific calpain, whose physiological functions are unclear. To elucidate these, we characterized nCL-2 in detail. Unexpectedly, nCL-2 was localized strictly to the surface mucus cells in the gastric epithelium and the mucus-secreting goblet cells in the duodenum. Yeast two-hybrid screening identified several nCL-2-interacting molecules. Of these, the beta-subunit of coatomer complex (beta-COP) occurs in the stomach pit cells and is proteolyzed by nCL-2 in vitro. Furthermore, beta-COP and nCL-2 co-expressed in COS7 cells co-localized in the Golgi, and Ca2+-ionophore stimulation caused the proteolysis of beta-COP near the linker region, resulting in the dissociation of beta-COP from the Golgi. These results strongly suggest novel functions for nCL-2 that involve the membrane trafficking of mucus cells via interactions with coat protein. 相似文献
82.
N-acetylglucosaminyltransferase (GnT)-IV catalyzes the formation of the GlcNAcβ1-4 branch on the GlcNAcβ1-2Manα1-3 arm of the
core structure of N-glycans. Two human GnT-IV isozymes (GnT-IVa and GnT-IVb) had been identified, which exhibit different expression profiles
among human tissues and cancer cell lines. To clarify the enzymatic properties of the respective enzymes, their kinetic parameters
were determined using recombinant full-length enzymes expressed in COS7 cells. The K
m of human GnT-IVb for UDP-GlcNAc was estimated to be 0.24 mM, which is 2-fold higher than that of human GnT-IVa. The K
m values of GnT-IVb for pyridylaminated (PA) acceptor sugar chains with different branch numbers were 3- to 6-fold higher than
those of GnT-IVa. To compare substrate specificities more precisely, we generated recombinant soluble enzymes of human GnT-IVa
and GnT-IVb with N-terminal flag tags. Both enzymes showed similar substrate specificities as determined using fourteen PA-sugar
chains. They preferred complex-type N-glycans over hybrid-types. Among the complex-type N-glycans tested, the relative activities of both enzymes were increased in proportion to the number of GlcNAc branches on
the Man α1-6 arm. The Man α1-6 arm of the acceptors was not essential for their activities because a linear pentasaccharide
lacking this arm, GlcNAcβ1-2Manα1-3Manβ1-4GlcNAcβ1-4 GlcNAc-PA, was a substrate for both enzymes. These results indicate that
human GnT-IVb exhibits the same acceptor substrate specificities as human GnT-IVa, although GnT-IVb has lower affinities for
donors or acceptors than GnT-IVa. This suggests that GnT-IVa is more active than GnT-IVb under physiological conditions and
that it primarily contributes to the biosynthesis of N-glycans. 相似文献
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85.
Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein 下载免费PDF全文
Tsukasa Mashima Akimasa Matsugami Fumiko Nishikawa Satoshi Nishikawa Masato Katahira 《Nucleic acids research》2009,37(18):6249-6258
RNA aptamers against bovine prion protein (bPrP) were obtained, most of the obtained aptamers being found to contain the r(GGAGGAGGAGGA) (R12) sequence. Then, it was revealed that R12 binds to both bPrP and its β-isoform with high affinity. Here, we present the structure of R12. This is the first report on the structure of an RNA aptamer against prion protein. R12 forms an intramolecular parallel quadruplex. The quadruplex contains G:G:G:G tetrad and G(:A):G:G(:A):G hexad planes. Two quadruplexes form a dimer through intermolecular hexad–hexad stacking. Two lysine clusters of bPrP have been identified as binding sites for R12. The electrostatic interaction between the uniquely arranged phosphate groups of R12 and the lysine clusters is suggested to be responsible for the affinity of R12 to bPrP. The stacking interaction between the G:G:G:G tetrad planes and tryptophan residues may also contribute to the affinity. One R12 dimer molecule is supposed to simultaneously bind the two lysine clusters of one bPrP molecule, resulting in even higher affinity. The atomic coordinates of R12 would be useful for the development of R12 as a therapeutic agent against prion diseases and Alzheimer''s disease. 相似文献
86.
Chisako Fujita Fumito Ichikawa Toshiaki Teratani Gen Murakami Takahiro Okada Masaki Shinohara Suguru Kawato Yoshihiro Ohta 《The Journal of steroid biochemistry and molecular biology》2009,117(1-3):50-55
Glucocorticoids are known to decrease intracellular ATP levels in the brain. This study was performed to investigate whether corticosterone at physiological levels depresses mitochondrial ATP production by directly acting on mitochondria. Mitochondria were isolated from immortalized hypothalamic GT1-7 neurons. ATP levels were determined using a luciferase–luciferin assay. When malate, α-ketoglutarate or pyruvate was used as a respiration substrate, corticosterone at ≥100 nM decreased ATP production by 10%. In contrast, corticosterone did not affect ATP production when succinate or N,N,N′,N′-tetramethyl-p-phenylenediamine + ascorbate were used. To investigate the specificity of corticosterone inhibition, we examined several steroids. All steroids tested suppressed mitochondrial ATP production by 10% at a concentration of 100 nM, in a manner similar to that of corticosterone. To examine the effects of corticosterone on GT1-7 cell physiology, we incubated GT1-7 cells with t-butyl hydroperoxide (t-BuOOH) with corticosterone. Corticosterone largely enhanced t-BuOOH-induced cell death. These results indicate that corticosterone non-specifically inhibits mitochondrial ATP production by suppressing electron transfer from NADH to the electron transfer chain through complex I. Partial inhibition of mitochondrial ATP production by corticosterone may contribute to oxidative stress-induced cell death. 相似文献
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Precise patterning of morphogen molecules and their accurate reading out are of key importance in embryonic development. Recent experiments have visualized distributions of proteins in developing embryos and shown that the gradient of concentration of Bicoid morphogen in Drosophila embryos is established rapidly after fertilization and remains stable through syncytial mitoses. This stable Bicoid gradient is read out in a precise way to distribute Hunchback with small fluctuations in each embryo and in a reproducible way, with small embryo-to-embryo fluctuation. The mechanisms of such stable, precise, and reproducible patterning through noisy cellular processes, however, still remain mysterious. To address these issues, here we develop the one- and three-dimensional stochastic models of the early Drosophila embryo. The simulated results show that the fluctuation in expression of the hunchback gene is dominated by the random arrival of Bicoid at the hunchback enhancer. Slow diffusion of Hunchback protein, however, averages out this intense fluctuation, leading to the precise patterning of distribution of Hunchback without loss of sharpness of the boundary of its distribution. The coordinated rates of diffusion and transport of input Bicoid and output Hunchback play decisive roles in suppressing fluctuations arising from the dynamical structure change in embryos and those arising from the random diffusion of molecules, and give rise to the stable, precise, and reproducible patterning of Bicoid and Hunchback distributions. 相似文献
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