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981.
Mikolajek H Kolstoe SE Pye VE Mangione P Pepys MB Wood SP 《Journal of molecular recognition : JMR》2011,24(2):371-377
The normal physiological roles of the phylogenetically conserved human plasma proteins C-reactive protein (CRP) and serum amyloid P component (SAP) are not known. Novel drugs targeting their ligand specificities are in clinical development as both proteins have significant pathophysiological effects, SAP in promoting amyloidosis and CRP in exacerbating ischemic injury. Both proteins bind to phosphoethanolamine and we show here that, under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. An explanation is provided by X-ray crystal structures that show SAP residue Tyr74 allowing additional hydrophobic protein-ligand interactions compared with the equivalent Thr76 of CRP. Docking simulations show many more low energy positions for phosphoethanolamine bound by CRP than by SAP and are consistent with the crystallographic and functional binding results. These fundamental observations on structure-activity relationships will aid the design of improved pentraxin targeting drugs. 相似文献
982.
Baolong Bao Valerie PestingerYousef I. Hassan Gloria E.O. BorgstahlCarol Kolar Janos Zempleni 《The Journal of nutritional biochemistry》2011,22(5):470-475
Holocarboxylase synthetase (HCS) mediates the binding of biotin to lysine (K) residues in histones H2A, H3 and H4; HCS knockdown disturbs gene regulation and decreases stress resistance and lifespan in eukaryotes. We tested the hypothesis that HCS interacts physically with histone H3 for subsequent biotinylation. Co-immunoprecipitation experiments were conducted and provided evidence that HCS co-localizes with histone H3 in human cells; physical interactions between HCS and H3 were confirmed using limited proteolysis assays. Yeast two-hybrid (Y2H) studies revealed that the N-terminal and C-terminal domains in HCS participate in H3 binding. Recombinant human HCS was produced and exhibited biological activity, as evidenced by biotinylation of its known substrate, recombinant p67. Recombinant histone H3.2 and synthetic H3-based peptides were also good targets for biotinylation by recombinant HCS (rHCS) in vitro, based on tracing histone-bound biotin with [3H]biotin, streptavidin and anti-biotin antibody. Biotinylation site-specific antibodies were generated and revealed that both K9 and K18 in H3 were biotinylated by HCS. Collectively, these studies provide conclusive evidence that HCS interacts directly with histone H3, causing biotinylation of K9 and K18. We speculate that the targeting of HCS to distinct regions in human chromatin is mediated by DNA sequence, biotin, RNA, epigenetic marks or chromatin proteins. 相似文献
983.
The PmrAB two-component system of enterobacteria regulates a number of genes whose protein products modify lipopolysaccharide (LPS). The LPS is modified during transport to the bacterial outer membrane (OM). A subset of PmrAB-mediated LPS modifications consists of the addition of phosphoethanolamine (pEtN) to lipid A by PmrC and to the core by CptA. In Salmonella enterica, pEtN modifications have been associated with resistance to polymyxin B and to excess iron. To investigate putative functions of pEtN modifications in Citrobacter rodentium, ΔpmrAB, ΔpmrC, ΔcptA, and ΔpmrC ΔcptA deletion mutants were constructed. Compared to the wild type, most mutant strains were found to be more susceptible to antibiotics that must diffuse across the LPS layer of the OM. All mutant strains also showed increased influx rates of ethidium dye across their OM, suggesting that PmrAB-regulated pEtN modifications affect OM permeability. This was confirmed by increased partitioning of the fluorescent dye 1-N-phenylnaphthylamine (NPN) into the OM phospholipid layer of the mutant strains. In addition, substantial release of periplasmic β-lactamase was observed for the ΔpmrAB and ΔpmrC ΔcptA strains, indicating a loss of OM integrity. This study attributes a new role for PmrAB-mediated pEtN LPS modifications in the maintenance of C. rodentium OM integrity. 相似文献
984.
985.
986.
Valerie A. Williams Peter T. Wolczanski Thomas R. Cundari 《Inorganica chimica acta》2011,369(1):203-214
While treatment of [(silox)2TaH2]2 (1, silox = tBu3SiO) with CO2 provided evidence for myriad hydride transfer products, related hydrides (silox)3TaH2 (15-Ta), (silox)3NbH (17), and [(silox)2WH]2 (20) afforded products of oxygen atom transfer (OAT) and CO reduction, such as (silox)3Ta(?2-CH2O) (16-Ta from 15-Ta) and [(silox)2W]2(μ-H)(μ-O)(μ-CH) (14, from 20). Low valent early metal derivatives (silox)3Ta (7) and (silox)3NbPMe3 (7-NbPMe3) generated (silox)3TaO (8-Ta) and (silox)3NbO (8-Nb), respectively, under high CO2 concentrations. Under low CO2 conditions, the products were the oxos and those derived from CO: (silox)3TaCCO (9-Ta) and (silox)3TaCCTa(silox)3 (10-Ta); (silox)3NbCCO (9-Nb) and (silox)3NbCCNb(silox)3 (10-Nb). On all occasions with CO present, preparations of 10-Nb yielded varying amounts of a similarly insoluble material tentatively characterized as (silox)3NbCONb(silox)3 (18-Nb). Metric parameters of a crystal structure determination purported to be of 10-Nb resemble those of 18-Nb according to calculations, but the bulk sample suggests cocrystallization of 9-Nb and 18-Nb. Calculations of 10-Ta, 10-Nb, and 18-Nb, including thermodynamics of dicarbide binding and CO scission help to understand the system. Since OAT is the major path for CO2 activation, it is suggested that CO2 reduction is best conducted by the water-gas shift reaction to produce CO, followed by Fischer-Tropsch processes. 相似文献
987.
Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling 总被引:1,自引:0,他引:1
In mammalian skin, multiple types of resident cells are required to create a functional tissue and support tissue homeostasis and regeneration. The cells that compose the epithelial stem cell niche for skin homeostasis and regeneration are not well defined. Here, we identify adipose precursor cells within the skin and demonstrate that their dynamic regeneration parallels the activation of skin stem cells. Functional analysis of adipocyte lineage cells in mice with defects in adipogenesis and in transplantation experiments revealed that intradermal adipocyte lineage cells are necessary and sufficient to drive follicular stem cell activation. Furthermore, we implicate PDGF expression by immature adipocyte cells in the regulation of follicular stem cell activity. These data highlight adipogenic cells as skin niche cells that positively regulate skin stem cell activity, and suggest that adipocyte lineage cells may alter epithelial stem cell function clinically. 相似文献
988.
Exchange of proteins at sorting endosomes is not only critical to numerous signaling pathways but also to receptor-mediated signaling and to pathogen entry into cells; however, how this process is regulated in synaptic vesicle cycling remains unexplored. In this work, we present evidence that loss of function of a single neuronally expressed GTPase activating protein (GAP), Skywalker (Sky) facilitates endosomal trafficking of synaptic vesicles at Drosophila neuromuscular junction boutons, chiefly by controlling Rab35 GTPase activity. Analyses of genetic interactions with the ESCRT machinery as well as chimeric ubiquitinated synaptic vesicle proteins indicate that endosomal trafficking facilitates the replacement of dysfunctional synaptic vesicle components. Consequently, sky mutants harbor a larger readily releasable pool of synaptic vesicles and show a dramatic increase in basal neurotransmitter release. Thus, the trafficking of vesicles via endosomes uncovered using sky mutants provides an elegant mechanism by which neurons may regulate synaptic vesicle rejuvenation and neurotransmitter release. 相似文献
989.
Abbaszadegan M Alum A Abbaszadegan H Stout V 《Applied and environmental microbiology》2011,77(15):5141-5148
The lack of efficient methods for concentrating viruses in water samples leads to underreporting of viral contamination in source water. A novel strategy for viral concentration was developed using the expression of target virus receptors on bacterial cells. Poliovirus type 1, the most studied enterovirus, was used as a surrogate for enteric viruses. The human poliovirus receptor (hPVR) gene was expressed on the surface of Escherichia coli cells by using the ice nucleation protein (INP) gene. The hPVR gene was ligated to the 3' end of the INP gene after the removal of the stop codon. The resulting open reading frame (ORF) was used for the projection of hPVR onto the outer membrane of E. coli. Gene expression was tested by SDS-PAGE, Western blot, and dot blot analyses, and virion capture ability was confirmed by transmission electron microscopy. The application of engineered E. coli cells for capturing viruses in 1-liter samples of source and drinking water resulted in 75 to 99% procedural recovery efficiency. Cell surface display of viral receptors on bacterial cells opens a new prospect for an efficient and inexpensive alternative tool for capturing and concentrating waterborne viruses in water samples. 相似文献
990.
Ghaffary SM Robert O Laurent V Lonnet P Margalé E van der Lee TA Visser RG Kema GH 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(5):741-754
The ascomycete Mycosphaerella graminicola is the causal agent of septoria tritici blotch (STB), one of the most destructive foliar diseases of bread and durum wheat
globally, particularly in temperate humid areas. A screening of the French bread wheat cultivars Apache and Balance with 30
M. graminicola isolates revealed a pattern of resistant responses that suggested the presence of new genes for STB resistance. Quantitative
trait loci (QTL) analysis of a doubled haploid (DH) population with five M. graminicola isolates in the seedling stage identified four QTLs on chromosomes 3AS, 1BS, 6DS and 7DS, and occasionally on 7DL. The QTL
on chromosome 6DS flanked by SSR markers Xgpw5176 and Xgpw3087 is a novel QTL that now can be designated as Stb18. The QTLs on chromosomes 3AS and 1BS most likely represent Stb6 and Stb11, respectively, and the QTLs on chromosome 7DS are most probably identical with Stb4 and Stb5. However, the QTL identified on chromosome 7DL is expected to be a new Stb gene that still needs further characterization. Multiple isolates were used and show that not all isolates identify all QTLs,
which clearly demonstrates the specificity in the M. graminicola–wheat pathosystem. QTL analyses were performed with various disease parameters. The development of asexual fructifications
(pycnidia) in the characteristic necrotic blotches of STB, designated as parameter P, identified the maximum number of QTLs. All other parameters identified fewer but not different QTLs. The segregation of
multiple QTLs in the Apache/Balance DH population enabled the identification of DH lines with single QTLs and multiple QTL
combinations. Analyses of the marker data of these DH lines clearly demonstrated the positive effect of pyramiding QTLs to
broaden resistance spectra as well as epistatic and additive interactions between these QTLs. Phenotyping of the Apache/Balance
DH population in the field confirmed the presence of the QTLs that were identified in the seedling stage, but Stb18 was inconsistently expressed and might be particularly effective in young plants. In contrast, an additional QTL for STB
resistance was identified on chromosome 2DS that is exclusively and consistently expressed in mature plants over locations
and time, but it was also strongly related with earliness, tallness as well as resistance to Fusarium head blight. Although
to date no Stb gene has been reported on chromosome 2D, the data provide evidence that this QTL is only indirectly related to STB resistance.
This study shows that detailed genetic analysis of contemporary commercial bread wheat cultivars can unveil novel Stb genes that can be readily applied in marker-assisted breeding programs. 相似文献