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Cecilia Andrésen Shah Jalal Daniel Aili Yi Wang Sohidul Islam Anngelica Jarl Bo Liedberg Bengt Wretlind Lars‐Göran Mårtensson Maria Sunnerhagen 《Protein science : a publication of the Protein Society》2010,19(4):680-692
The self‐assembling MexA‐MexB‐OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR‐wt as well as a selected set of MDR single mutants distant from the proposed DNA‐binding helix. Although DNA affinity and MexA‐MexB‐OprM repression were both drastically impaired in the selected MexR‐MDR mutants, MexR‐wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR‐MDR mutants, secondary structure content and oligomerization properties were very similar to MexR‐wt despite their lack of DNA binding. Despite this, the MexR‐MDR mutants showed highly varying stabilities compared with MexR‐wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA‐binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR‐wt in both free and DNA‐bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations—stability, domain interactions, and internal hydrophobic surfaces—are also critical for the regulation of MexR DNA binding. 相似文献
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Kazi AS Lotfi S Goncharova EA Tliba O Amrani Y Krymskaya VP Lazaar AL 《American journal of physiology. Lung cellular and molecular physiology》2004,286(3):L539-L545
In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-beta, IL-1beta, and PGE(2). We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma. 相似文献
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While conducting experiments to investigate antimicrobial peptides of amphibians living in the Yunnan-Sichuan region of southwest China, a new family of antimicrobial peptides was identified from skin secretions of the rufous-spotted torrent frog, Amolops loloensis. Members of the new peptide family named amolopins are composed of 18 amino acids with a unique sequence, for example, NILSSIVNGINRALSFFG. By BLAST search, amolopins did no show similarity to any known peptides. Among the tested microorganisms, native and synthetic peptides only showed antimicrobial activities against Staphylococcus aureus ATCC2592 and Bacillus pumilus, no effects on other microorganisms. The CD spectroscopy showed that it adopted a structure of random combined with beta-sheet in water, Tris-HCl or Tris-HCl-SDS. Several cDNAs encoding amolopins were cloned from the skin cDNA library of A. loloensis. The precursors of amolopin are composed of 62 amino acid residues including predicted signal peptides, acidic propieces, and mature antimicrobial peptides. The preproregion of amolopin precursor comprises a hydrophobic signal peptide of 22 residues followed by an 18 residue acidic propiece which terminates by a typical prohormone processing signal Lys-Arg. The preproregions of precursors are very similar to other amphibian antimicrobial peptide precursors but the mature amolopins are different from other antimicrobial peptide families. The remarkable similarity of preproregions of precursors that give rise to very different antimicrobial peptides in distantly related frog species suggests that the corresponding genes form a multigene family originating from a common ancestor. 相似文献
4.
Zhao Wei Fan Aili Tarcz Sylwia Zhou Kang Yin Wen-Bing Liu Xiao-Qing Li Shu-Ming 《Applied microbiology and biotechnology》2017,101(5):1989-1998
Applied Microbiology and Biotechnology - The fungal cyclic dipeptide prenyltransferase FtmPT1 from Aspergillus fumigatus catalyzes a regular C2-prenylation of brevianamide F (cyclo-l-Trp-l-Pro) and... 相似文献
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Foxtail Millet CBL4 (SiCBL4) Interacts with SiCIPK24, Modulates Plant Salt Stress Tolerance 总被引:1,自引:0,他引:1
Yumin Zhang Jingjing Linghu Dong Wang Xi Liu Aili Yu Fengting Li Jinfeng Zhao Tianyong Zhao 《Plant Molecular Biology Reporter》2017,35(6):634-646
The calcineurin B-like (CBL) protein and the CBL-interacting protein kinase (CIPK) signaling pathway play important roles in plant abiotic stress tolerance. To investigate the molecular mechanism of salt stress tolerance of foxtail millet, SiCBL4 and SiCIPK24 were identified and functionally characterized. Both SiCBL4 and SiCIPK24 were induced by salt, abscisic acid (ABA), methyl viologen (MV), and heat shock stress in foxtail millet seedlings. Yeast two-hybrid and bimolecular fluorescence complementation assay showed that SiCBL4 interacted with SiCIPK24. The mutation of the N-myristoylation site of SiCBL4 changed the sub-cellular localization of SiCBL4 and directed the SiCBL4-SiCIPK24 protein complex from plasma membrane to cytoplasm, and disrupted its function in plant salt stress tolerance. Overexpression of SiCBL4 or SiCIPK24 in Arabidopsis sos3-1 or sos2-1 mutant plants rescued the mutant salt hypersensitivity phenotype. In addition, overexpression of SiCIPK24 also enhanced the salt stress tolerance of Arabidopsis wild-type plants. This work helps to understand the structure and function of the foxtail millet CBL and CIPK genes and confirmed that the foxtail millet CBL-CIPK pathway can be manipulated to enhance the plant salt stress tolerance. 相似文献
7.
The kidney fat was histologically examined of 27 spontaneously dead lambs of which 14 had starved. The lambs were born with mature fat, but in young animals a starvation period of more than 24 hrs. reduced the fat tissues and changed its cells towards the embryonal type built up of preadipocytes. These cells were smaller than the mature fat cells. Nucleus was large, round and situated in the centre of the cell. The slight eosinophilic, strongly diminished cytoplasm was some granulated and had some small fat droplets. The starvation changes of fat cells did not depend on the weight of animals or on the age of lambs less than two weeks. 相似文献
8.
A series of 52 young male white laboratory mice were starved for a maximum of five days, and 45 normally fed animals were used as controls. A group of experimental animals and a corresponding control group were sacrificed after two, three, and four days' starvation and after six, 12 and 17 days' refeeding. Even after two days the animals had lost weight, and the liver cells had diminished highly significantly. A return to the initial values was noted after 12 days' refeeding. In the experimental animals a strong negative correlation was noted between the cell count per field and body weight (r =–0.712, b =–7.520), while no such correlation was observed for the controls. The volume of the liver cells was reduced by 61.7 %, the volume of their nuclei by 16.2 % after four days' starvation. After two to three days' starvation the liver cells often showed a slight accumulation of fat. Mitoses were frequent in the liver cells during the stage of regeneration, when the cells had attained the same size as in the controls. 相似文献
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