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971.
Eike Christian Schulz Martin Frank Martina Mühlenhoff Rita Gerardy-Schahn Ralf Ficner 《Journal of molecular biology》2010,397(1):341-351
An α-2,8-linked polysialic acid (polySia) capsule confers immune tolerance to neuroinvasive, pathogenic prokaryotes such as Escherichia coli K1 and Neisseria meningitidis and supports host infection by means of molecular mimicry. Bacteriophages of the K1 family, infecting E. coli K1, specifically recognize and degrade this polySia capsule utilizing tailspike endosialidases. While the crystal structure for the catalytic domain of the endosialidase of bacteriophage K1F (endoNF) has been solved, there is yet no structural information on the mode of polySia binding and cleavage available. The crystal structure of activity deficient active-site mutants of the homotrimeric endoNF cocrystallized with oligomeric sialic acid identified three independent polySia binding sites in each endoNF monomer. The bound oligomeric sialic acid displays distinct conformations at each site. In the active site, a Sia3 molecule is bound in an extended conformation representing the enzyme-product complex. Structural and biochemical data supported by molecular modeling enable to propose a reaction mechanism for polySia cleavage by endoNF. 相似文献
972.
Latifa ElAntak Susan Wagner Anna Herrmannová Martina Karásková Peter J. Lukavsky Leoš Valášek 《Journal of molecular biology》2010,396(4):1097-1825
Despite recent progress in our understanding of the numerous functions of individual subunits of eukaryotic translation initiation factor (eIF) 3, little is known on the molecular level. Using NMR spectroscopy, we determined the first solution structure of an interaction between eIF3 subunits. We revealed that a conserved tryptophan residue in the human eIF3j N-terminal acidic motif (NTA) is held in the helix α1 and loop 5 hydrophobic pocket of the human eIF3b RNA recognition motif (RRM). Mutating the corresponding “pocket” residues in its yeast orthologue reduces cellular growth rate, eliminates eIF3j/HCR1 association with eIF3b/PRT1 in vitro and in vivo, affects 40S occupancy of eIF3, and produces a leaky scanning defect indicative of a deregulation of the AUG selection process. Unexpectedly, we found that the N-terminal half of eIF3j/HCR1 containing the NTA is indispensable and sufficient for wild-type growth of yeast cells. Furthermore, we demonstrate that deletion of either j/HCR1 or its N-terminal half only, or mutation of the key tryptophan residues results in the severe leaky scanning phenotype partially suppressible by overexpressed eIF1A, which is thought to stabilize properly formed preinitiation complexes at the correct start codon. These findings indicate that eIF3j/HCR1 remains associated with the scanning preinitiation complexes and does not dissociate from the small ribosomal subunit upon mRNA recruitment, as previously believed. Finally, we provide further support for earlier mapping of the ribosomal binding site for human eIF3j by identifying specific interactions of eIF3j/HCR1 with small ribosomal proteins RPS2 and RPS23 located in the vicinity of the mRNA entry channel. Taken together, we propose that eIF3j/HCR1 closely cooperates with the eIF3b/PRT1 RRM and eIF1A on the ribosome to ensure proper formation of the scanning-arrested conformation required for stringent AUG recognition. 相似文献
973.
As anthropogenic N deposition has been suspected to be the main reason for the decline of macromycetous sporocarp production
in forest ecosystems, various N-fertilization experiments were started in the mid 1990s. The dynamics of ectomycorrhizal (root-inhabiting)
and terricolous saprobic (litter-inhabiting) fungal communities were studied by exhaustive sporocarp inventories in a substitution
Norway spruce (Picea abies) forest in two 256-m2 plots sampled for periods of 1 week at 1-m2 resolution between 1994 and 2007. N was added to the soil twice per year in one plot from the fourth year onwards. The effects
of N input and time on aboveground fungal communities were assessed using redundancy analysis, principal response curves and
non-parametric multivariate ANOVA. Results of this long-term experiment revealed that both ectomycorrhizal and saprobic fungal
communities responded to an increase in soil N input. The ectomycorrhizal community reacted by a fast decrease in sporocarp
production and in species richness, whereas the saprobic community was less affected. The response was highly species specific,
especially for the saprobic community. The difference in species composition between control and fertilized plots was significant
after 1 year of N addition for ectomycorrhizal fungi and only after 3 years for saprobic fungi. An aging effect affected sporocarp
production in the whole area. For both communities, this unidirectional drift in species composition was as important as the
treatment effect. This result highlights the importance of considering the respective role of treatment and year effects in
long-term field experiments on fungal communities. 相似文献
974.
Fabian Buller Martina Steiner Jörg Scheuermann Luca Mannocci Ina Nissen Manuel Kohler Christian Beisel Dario Neri 《Bioorganic & medicinal chemistry letters》2010,20(14):4188-4192
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs. 相似文献
975.
Yinfa Yan Ping Zhou David P. Rotella Rolf Feenstra Chris G. Kruse Jan-Hendrik Reinders Martina van der Neut Margaret Lai Jean Zhang Dianne M. Kowal Tikva Carrick Karen L. Marquis Mark H. Pausch Albert J. Robichaud 《Bioorganic & medicinal chemistry letters》2010,20(9):2983-2986
A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure–activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity. 相似文献
976.
977.
Roesch-Ely M Schnölzer M Nees M Plinkert PK Bosch FX 《Archives of physiology and biochemistry》2010,116(4-5):218-226
We reasoned that micro-dissection of tumour cells for protein expression studies should be omitted since tumour-stroma interactions are an important part of the biology of solid tumours. To study such interactions in head and neck squamous cell carcinoma (HNSCC) development, we generated reference protein spectra for normal squamous epithelium and connective tissue by SELDI-TOF-MS. Calgranulins A and B, Annexin1 and Histone H4 were found to be strongly enriched in the epithelium. The alpha-defensins 1-3 and the haemoglobin subunits were identified in the connective tissue. Tumour-distant epithelia, representing early pre-malignant lesions, showed up-regulated expression of the stromal alpha-defensins, whereas the epithelial Annexin 1 was down-regulated. Thus, tumour microenvironment interactions occur very early in the carcinogenic process. These data demonstrate that omitting micro-dissection is actually beneficial for studying changes in protein expression during development and progression of solid tumours. 相似文献
978.
Liehr T Karamysheva T Merkas M Brecevic L Hamid AB Ewers E Mrasek K Kosyakova N Weise A 《Current Genomics》2010,11(6):432-439
Somatic mosaicism is something that is observed in everyday lives of cytogeneticists. Chromosome instability is one of the leading causes of large-scale genome variation analyzable since the correct human chromosome number was established in 1956. Somatic mosaicism is also a well-known fact to be present in cases with small supernumerary marker chromosomes (sSMC), i.e. karyotypes of 47,+mar/46. In this study, the data available in the literature were collected concerning the frequency mosaicism in different subgroups of patients with sSMC. Of 3124 cases with sSMC 1626 (52%) present with somatic mosaicism. Some groups like patients with Emanuel-, cat-eye- or i(18p)- syndrome only tend rarely to develop mosaicism, while in Pallister-Killian syndrome every patient is mosaic. In general, acrocentric and non-acrocentric derived sSMCs are differently susceptible to mosaicism; non-acrocentric derived ones are hereby the less stable ones. Even though, in the overwhelming majority of the cases, somatic mosaicism does not have any detectable clinical effects, there are rare cases with altered clinical outcomes due to mosaicism. This is extremely important for prenatal genetic counseling. Overall, as mosaicism is something to be considered in at least every second sSMC case, array-CGH studies cannot be offered as a screening test to reliably detect this kind of chromosomal aberration, as low level mosaic cases and cryptic mosaics are missed by that. 相似文献
979.
Barbara C. B?ck Katrin E. Tagscherer Anne Fassl Anika Kr?mer Ina Oehme Hans-Walter Zentgraf Martina Keith Wilfried Roth 《The Journal of biological chemistry》2010,285(28):21644-21654
PEA-15/PED (phosphoprotein enriched in astrocytes 15 kDa/phosphoprotein enriched in diabetes) is a death effector domain-containing protein which is known to modulate apoptotic cell death. The mechanism by which PEA-15 inhibits caspase activation and increases ERK (extracellular-regulated kinase) activity is well characterized. Here, we demonstrate that PEA-15 is not only pivotal in the activation of the ERK pathway but also modulates JNK (c-Jun N-terminal kinase) signaling. Upon overexpression of PEA-15 in malignant glioma cells, JNK is potently activated. The PEA-15-induced JNK activation depends on the phosphorylation of PEA-15 at both phosphorylation sites (serine 104 and serine 116). The activation of JNK is substantially inhibited by siRNA-mediated down-regulation of endogenous PEA-15. Moreover, we demonstrate that glioma cells overexpressing PEA-15 show increased signs of autophagy in response to classical autophagic stimuli such as ionizing irradiation, serum deprivation, or rapamycin treatment. In contrast, the non-phosphorylatable mutants of PEA-15 are not capable of promoting autophagy. The inhibition of JNK abrogates the PEA-15-mediated increase in autophagy. In conclusion, our data show that PEA-15 promotes autophagy in glioma cells in a JNK-dependent manner. This might render glioma cells more resistant to adverse stimuli such as starvation or ionizing irradiation. 相似文献
980.
Sara A Collins Alexandra Buhles Martina F Scallan Patrick T Harrison Deirdre M O'Hanlon Gerald C O'Sullivan Mark Tangney 《Genetic vaccines and therapy》2010,8(1):1-13