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61.
Giovannini D Späth S Lacroix C Perazzi A Bargieri D Lagal V Lebugle C Combe A Thiberge S Baldacci P Tardieux I Ménard R 《Cell host & microbe》2011,10(6):591-602
During invasion, apicomplexan parasites form an intimate circumferential contact with the host cell, the tight junction (TJ), through which they actively glide. The TJ, which links the parasite motor to the host cell cytoskeleton, is thought to be composed of interacting apical membrane antigen 1 (AMA1) and rhoptry neck (RON) proteins. Here we find that, in Plasmodium berghei, while both AMA1 and RON4 are important for merozoite invasion of erythrocytes, only RON4 is required for sporozoite invasion of hepatocytes, indicating that RON4 acts independently of AMA1 in the sporozoite. Further, in the Toxoplasma gondii tachyzoite, AMA1 is dispensable for normal RON4 ring and functional TJ assembly but enhances tachyzoite apposition to the cell and internalization frequency. We propose that while the RON proteins act at the TJ, AMA1 mainly functions on the zoite surface to permit correct attachment to the cell, which may facilitate invasion depending on the zoite-cell combination. 相似文献
62.
63.
Chrysoula Vasileiou Wenjing Wang Xiaofei Jia Kin Sing Stephen Lee Camille T. Watson James H. Geiger Babak Borhan 《Proteins》2009,77(4):812-822
Cellular Retinoic Acid Binding Protein II (CRABPII) has been reengineered to specifically bind and react with all‐trans‐retinal to form a protonated Schiff base. Each step of this process has been dissected and four residues (Lys132, Tyr134, Arg111, and Glu121) within the CRABPII binding site have been identified as crucial for imine formation and/or protonation. The precise role of each residue has been examined through site directed mutagenesis and crystallographic studies. The crystal structure of the R132K:L121E‐CRABPII (PDB‐3I17) double mutant suggests a direct interaction between engineered Glu121 and the native Arg111, which is critical for both Schiff base formation and protonation. Proteins 2009. © 2009 Wiley‐Liss, Inc. 相似文献
64.
Elian Dupré Julien Herrou Marc F. Lensink René Wintjens Alexey Vagin Andrey Lebedev Sean Crosson Vincent Villeret Camille Locht Rudy Antoine Fran?oise Jacob-Dubuisson 《PLoS pathogens》2015,11(3)
Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, the TCS BvgAS controls the virulence regulon, and is therefore critical for pathogenicity. BvgS is a prototypical TCS sensor-kinase with tandem periplasmic Venus flytrap (VFT) domains. VFT are bi-lobed domains that typically close around specific ligands using clamshell motions. We report the X-ray structure of the periplasmic moiety of BvgS, an intricate homodimer with a novel architecture. By combining site-directed mutagenesis, functional analyses and molecular modeling, we show that the conformation of the periplasmic moiety determines the state of BvgS activity. The intertwined structure of the periplasmic portion and the different conformation and dynamics of its mobile, membrane-distal VFT1 domains, and closed, membrane-proximal VFT2 domains, exert a conformational strain onto the transmembrane helices, which sets the cytoplasmic moiety in a kinase-on state by default corresponding to the virulent phase of the bacterium. Signaling the presence of negative signals perceived by the periplasmic domains implies a shift of BvgS to a distinct state of conformation and activity, corresponding to the avirulent phase. The response to negative modulation depends on the integrity of the periplasmic dimer, indicating that the shift to the kinase-off state implies a concerted conformational transition. This work lays the bases to understand virulence regulation in Bordetella. As homologous sensor-kinases control virulence features of diverse bacterial pathogens, the BvgS structure and mechanism may pave the way for new modes of targeted therapeutic interventions. 相似文献
65.
Wilhelm Salzberger Wilfredo F. Garcia-Beltran Haley Dugan Supreetha Gubbala Camille Simoneau Simon B. Gressens Stephanie Jost Marcus Altfeld 《PloS one》2015,10(12)
Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I N-glycan has on KIR:HLA interactions and NK cell function. We focused on HLA-B*57:01 and its interaction with KIR3DL1, which has been shown to play a critical role in determining the progression of a number of human diseases, including human immunodeficiency virus-1 infection. 721.221 cells stably expressing HLA-B*57:01 were treated with a panel of glycosylation enzyme inhibitors, and HLA class I expression and KIR3DL1 binding was quantified. In addition, the functional outcomes of HLA-B*57:01 N-glycan disruption/modulation on KIR3DL1ζ+ Jurkat reporter cells and primary human KIR3DL1+ NK cells was assessed. Different glycosylation enzyme inhibitors had varying effects on HLA-B*57:01 expression and KIR3DL1-Fc binding. The most remarkable effect was that of tunicamycin, an inhibitor of the first step of N-glycosylation, which resulted in significantly reduced KIR3DL1-Fc binding despite sustained expression of HLA-B*57:01 on 721.221 cells. This effect was paralleled by decreased activation of KIR3DL1ζ+ Jurkat reporter cells, as well as increased degranulation of primary human KIR3DL1+ NK cell clones when encountering HLA-B*57:01-expressing 721.221 cells that were pre-treated with tunicamycin. Overall, these results demonstrate that N-glycosylation of HLA class I is important for KIR:HLA binding and has an impact on NK cell function. 相似文献
66.
Traditional approaches to understanding cognition in children with epilepsy (CWE) involve cross-sectional or prospective examination of diverse test measures, an approach that does not inform the interrelationship between different abilities or how interrelationships evolve prospectively. Here we utilize graph theory techniques to interrogate the development of cognitive landmarks in CWE and healthy controls (HC) using the two-year percentage change across 20 tests. Additionally, we characterize the development of cognition using traditional analyses, showing that CWE perform worse at baseline, develop in parallel with HC, statically maintaining cognitive differences two years later. Graph analyses, however, showed CWE to exhibit both lower integration and segregation in development of their cognitive networks compared to HC. In conclusion, graph analyses of neuropsychological data capture a dynamic and changing complexity in the interrelationships among diverse cognitive skills, maturation of the cognitive network over time, and the nature of differences between normally developing children and CWE. 相似文献
67.
Vanessa Gouge-Ibert Camille Pierry Florent Poulain Anne-Lise Serre Céline Largeau Virginie Escriou Daniel Scherman Philippe Jubault Jean-Charles Quirion Eric Leclerc 《Bioorganic & medicinal chemistry letters》2010,20(6):1957-1960
The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH2-glycopeptides already reported to act as sLex mimics. The α and β anomers of these CF2-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of α- and β-pyranose and α- and β-furanose forms. These molecules showed inhibitory activities comparable to their CH2 counterparts with a moderate influence of the pseudo-anomeric center configuration. 相似文献
68.
Patricia Ann Okubara Camille M. Steber Victor L. DeMacon Nathalie L. Walter Timothy C. Paulitz Kimberlee K. Kidwell 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(2):293-303
The necrotrophic root pathogens Rhizoctonia solani AG-8 and R. oryzae cause Rhizoctonia root rot and damping-off, yield-limiting diseases that pose barriers to the adoption of conservation tillage
in wheat production systems. Existing control practices are only partially effective, and natural genetic resistance to Rhizoctonia has not been identified in wheat or its close relatives. We report the first genetic resistance/tolerance to R. solani AG-8 and R. oryzae in wheat (Triticum aestivum L. em Thell) germplasm ‘Scarlet-Rz1’. Scarlet-Rz1 was derived from the allohexaploid spring wheat cultivar Scarlet using
EMS mutagenesis. Tolerant seedlings displayed substantial root and shoot growth after 14 days in the presence of 100–400 propagules
per gram soil of R. solani AG-8 and R. oryzae in greenhouse assays. BC2F4 individuals of Scarlet-Rz1 showed a high and consistent degree of tolerance. Seedling tolerance was transmissible and appeared
to be dominant or co-dominant. Scarlet-Rz1 is a promising genetic resource for developing Rhizoctonia-tolerant wheat cultivars because the tolerance trait immediately can be deployed into wheat breeding germplasm through cross-hybridization,
thereby avoiding difficulties with transfer from secondary or tertiary relatives as well as constraints associated with genetically
modified plants. Our findings also demonstrate the utility of chemical mutagenesis for generating tolerance to necrotrophic
pathogens in allohexaploid wheat.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
P. A. Okubara and C. M. Steber contributed equally to this work. 相似文献
69.
Dominique Champion Camille Loupiac Denise Simatos Peter Lillford Philippe Cayot 《Food biophysics》2011,6(1):160-169
The state of water in foodstuffs is a guiding principle in food design, and the equilibrium concept of water activity (Aw)
is ubiquitous. It is regarded as a primary variable or “hurdle” in preservation technology, and a key variable influencing
chemical reaction during storage. However, the amount of water in any system differs as function of water activity depending
whether it is determined by water sorption or desorption. Even though this hysteresis behaviour has already been described
in the literature, no physical interpretation of its origin has yet been proposed with respect to detailed molecular organisation.
This work shows, for two different food powders, gluten and a milk-based product that the hysteresis disappears when either
go through their glass transition. A more complete DSC analysis for gluten during different sorption/desorption cycles demonstrates
that the hysteresis is dependent on the ageing of the material, which evolves in the glassy state and is induced by structural
relaxation. 相似文献
70.
Taillé C El-Benna J Lanone S Boczkowski J Motterlini R 《The Journal of biological chemistry》2005,280(27):25350-25360
Carbon monoxide (CO), one of the end products of heme oxygenase activity, inhibits smooth muscle proliferation by decreasing ERK1/2 phosphorylation and cyclin D1 expression, a signaling pathway that is known to be modulated by reactive oxygen species (ROS) in airway smooth muscle cells (ASMCs). Two important sources of ROS involved in cell signaling are the membrane NAD(P)H oxidase and the mitochondrial respiratory chain. Thus, that CO could modulate redox signaling in ASMCs by interacting with the heme moiety of NAD(P)H oxidase and/or the respiratory chain is a plausible hypothesis. Here we show that a recently identified carbon monoxide-releasing molecule, [Ru(CO)3Cl2]2 (or CORM-2) 1) inhibits NAD(P)H oxidase cytochrome b558 activity, 2) increases oxidant production by the mitochondria, and 3) inhibits ASMC proliferation and phosphorylation of the ERK1/2 mitogen-activated protein kinase and expression of cyclin D1, two critical pathways involved in muscle proliferation. No such effects were observed with the negative control (Ru(Me2SO)4Cl2), which does not contain CO groups. Because both diphenylene iodinium or apocynin (inhibitors of NAD(P)H oxidase) and rotenone (a molecule that increases mitochondrial ROS production by blocking the respiratory chain) mimicked the effect of CORM-2 on cyclin D1 expression and ASMC proliferation, the antiproliferative effect of CORM-2 is probably related to inhibition of cytochromes on both NAD(P)H oxidase and the respiratory chain. The involvement of increased mitochondria-derived oxidants is substantiated by the findings showing that the antioxidant N-acetylcysteine partially inhibited the effects of CORM-2. This study provides a new mechanism to explain redox signaling by CO. 相似文献