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Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis 下载免费PDF全文
Rothbächer U Laurent MN Deardorff MA Klein PS Cho KW Fraser SE 《The EMBO journal》2000,19(5):1010-1022
Dishevelled (Dsh) induces a secondary axis and can translocate to the membrane when activated by Frizzleds; however, dominant-negative approaches have not supported a role for Dsh in primary axis formation. We demonstrate that the Dsh protein is post-translationally modified at the dorsal side of the embryo: timing and position of this regulation suggests a role of Dsh in dorsal-ventral patterning in Xenopus. To create functional links between these properties of Dsh we analyzed the influence of endogenous Frizzleds and the Dsh domain dependency for these characteristics. Xenopus Frizzleds phosphorylate and translocate Xdsh to the membrane irrespective of their differential ectopic axes inducing abilities, showing that translocation is insufficient for axis induction. Dsh deletion analysis revealed that axis inducing abilities did not segregate with Xdsh membrane association. The DIX region and a short stretch at the N-terminus of the DEP domain are necessary for axis induction while the DEP region is required for Dsh membrane association and its phosphorylation. In addition, Dsh forms homomeric complexes in embryos suggesting that multimerization is important for its proper function. 相似文献
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We report the complete genome sequence of Pseudomonas aeruginosa siphophage MP1412, which displays synteny to those of P. aeruginosa phages M6 and YuA. However, the presence of two homing endonucleases of the GIY-YIG family is unique to MP1412, suggesting their unique role in the phage life cycle of the bacterial host. 相似文献
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An enteric bacterium, Escherichia coli W26 (KACC 16630), was isolated from feces from a healthy cow in South Korea. Here, we report the draft genome sequence of the isolate, which is closely affiliated with commensal strains belonging to E. coli phylogroup B1. 相似文献
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We have used polarized absorbance to observe the process of monomer accretion and polymer alignment which occurs in domains of sickle hemoglobin that are formed and maintained by laser photolysis. These diffusion and alignment processes have been studied as a function of initial concentration and temperature (initial and final), as well as beam size and domain number. Monomers are found to diffuse into growing polymer domains with a rate that is essentially temperature and concentration independent, but which depends on the size of the final domain boundaries, and the number of domains within a boundary. The final concentrations achieved are very close to those found in packed centrifugation experiments (50-55 g/dl) and are approximately independent of starting temperature and concentration. The influx of monomers is accompanied by polymer alignment, and the amount aligned is proportional to the amount diffused throughout the process. We propose that polymer alignment controls the influx of added monomers into the growing domain. 相似文献
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Hyung-Jun Kwon Young Bae Ryu Young-Min Kim Naaleum Song Cha Young Kim Mun-Chual Rho Jae-Ho Jeong Kyoung-Oh Cho Woo Song Lee Su-Jin Park 《Bioorganic & medicinal chemistry》2013,21(15):4706-4713
Despite the prepdominat agent causing severe entero-pathogenic diarrhea in swine, there are no effective therapeutical treatment of porcine epidemic diarrhea virus (PEDV). In this study, we evaluated the antiviral activity of five phlorotannins isolated from Ecklonia cava (E. cava) against PEDV. In vitro antiviral activity was tested using two different assay strategies: (1) blockage of the binding of virus to cells (simultaneous-treatment assay) and (2) inhibition of viral replication (post-treatment assay). In simultaneous-treatment assay, compounds 2–5 except compound 1 exhibited antiviral activities of a 50% inhibitory concentration (IC50) with the ranging from 10.8 ± 1.4 to 22.5 ± 2.2 μM against PEDV. Compounds 1–5 were completely blocked binding of viral spike protein to sialic acids at less than 36.6 μM concentrations by hemagglutination inhibition. Moreover, compounds 4 and 5 of five phlorotannins inhibited viral replication with IC50 values of 12.2 ± 2.8 and 14.6 ± 1.3 μM in the post-treatment assay, respectively. During virus replication steps, compounds 4 and 5 exhibited stronger inhibition of viral RNA and viral protein synthesis in late stages (18 and 24 h) than in early stages (6 and 12 h). Interestingly, compounds 4 and 5 inhibited both viral entry by hemagglutination inhibition and viral replication by inhibition of viral RNA and viral protein synthesis, but not viral protease. These results suggest that compounds isolated from E. cava have strong antiviral activity against PEDV, inhibiting viral entry and/or viral replication, and may be developed into natural therapeutic drugs against coronavirus infection. 相似文献
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Farah El-Turk Bruno Fauvet Amer Ashrafi Hajer Ouertatani-Sakouhi Min-Kyu Cho Marilisa Neri Michele Cascella Ursula Rothlisberger Florence Pojer Markus Zweckstetter Hilal Lashuel 《PloS one》2012,7(9)
Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF’s trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G), alanine (L46A) and phenylalanine (L46F), and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state. 相似文献
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Gurdev S. Khush Sichul Lee Jung-Il Cho Jong-Seong Jeon 《Plant biotechnology reports》2012,6(3):195-202
Micronutrient deficiencies affect approximately 3 billion people worldwide. Malnutrition hinders the development of human potential and social and economic development in developing countries. The World Health Organization (WHO) and the Consultative Group on International Agricultural Research (CGIAR) have made fighting micronutrient deficiencies, known as hidden hunger, a high priority. Deficiencies of the micronutrients, such as iron, zinc, and vitamin A, are the most devastating among the world’s poor. WHO emphasizes nutrient supplementation and food fortification to address the malnutrition. CGIAR has placed a greater emphasis on biofortification through the HarvestPlus challenge program, and improved micronutrient content of the staple crops (rice, wheat, maize, beans, cassava, pearl millet, and sweet potato) through breeding and biotechnological approaches. An excellent example of biotechnology application is the development of ‘golden rice’ with adequate levels of a provitamin A, β-carotene. The Africa Harvest and the BioCassava Plus programs, respectively, are developing sorghum and cassava with improved nutritional quality. Here, we summarize current strategies of crop biofortification and future prospects towards the development of biofortified crops. 相似文献