排序方式: 共有50条查询结果,搜索用时 15 毫秒
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Zhiwei Yang Yizhen Zhao Dongxiao Hao Shunlin Ren Xiaohui Yuan Lingjie Meng 《Journal of biomolecular structure & dynamics》2020,38(7):1918-1926
AbstractPeroxisome proliferator-activated receptor gamma (PPARγ) has recently been identified as an attractive target for atherosclerosis intervention. Given potential relevance of 5-cholesten-3β, 25-diol, 3-sulphate (CHOS) and PPARγ, an integrated docking method was used to study their interaction mechanisms, with the full considerations to distinct CHOS conformations and dynamic ensembles of PPARγ ligand-binding domain (PPARγ-LBD). The results revealed that this novel platform is satisfactory to the accurate determination of binding profiles, and the binding pattern of CHOS is rather similar as those of current PPARγ full/partial agonists. CHOS contributes to the stabilization of the AF2 and β-sheet surfaces of PPARγ-LBD and promotes the configuration adjustment of Ω loop, in order to inhibit the Cdk5-mediated PPARγ phosphorylation. Nonetheless, there are clear differences in term of occupation of full or partial agonist-like binding models. The energetic and geometric analyses further revealed that CHOS may be fond of partial agonist-like binding, and its sulfonic group and carbon skeleton are helpful for the binding process. We hope that the results will aid our understanding of recognitions involving CHOS with PPARγ-LBD and warrant the further aspects to pharmacological experiments.Communicated by Ramaswamy H. Sarma 相似文献
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Jiao Hu Zenglei Hu Yiqun Mo Qiwen Wu Zhu Cui Zhiqiang Duan Junqing Huang Hongzhi Chen Yuxin Chen Min Gu Xiaoquan Wang Shunlin Hu Huimou Liu Wenbo Liu Xiaowen Liu Xiufan Liu 《Journal of virology》2013,87(20):11063-11075
Most highly pathogenic avian influenza A viruses cause only mild clinical signs in ducks, serving as an important natural reservoir of influenza A viruses. However, we isolated two H5N1 viruses that are genetically similar but differ greatly in virulence in ducks. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is low pathogenic. To determine the genetic basis for the high virulence of CK10 in ducks, we generated a series of single-gene reassortants between CK10 and GS10 and tested their virulence in ducks. Expression of the CK10 PA or hemagglutinin (HA) gene in the GS10 context resulted in increased virulence and virus replication. Conversely, inclusion of the GS10 PA or HA gene in the CK10 background attenuated the virulence and virus replication. Moreover, the PA gene had a greater contribution. We further determined that residues 101G and 237E in the PA gene contribute to the high virulence of CK10. Mutations at these two positions produced changes in virulence, virus replication, and polymerase activity of CK10 or GS10. Position 237 plays a greater role in determining these phenotypes. Moreover, the K237E mutation in the GS10 PA gene increased PA nuclear accumulation. Mutant GS10 viruses carrying the CK10 HA gene or the PA101G or PA237E mutation induced an enhanced innate immune response. A sustained innate response was detected in the brain rather than in the lung and spleen. Our results suggest that the PA and HA gene-mediated high virus replication and the intense innate immune response in the brain contribute to the high virulence of H5N1 virus in ducks. 相似文献
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【目的】探讨新城疫病毒(Newcastle disease virus,NDV)基质(matrix,M)蛋白和禽细胞核磷蛋白B23.1在HEK-293T细胞中的相互作用。【方法】分别参照GenBank中NDV JS/5/05/Go株全基因序列(JN631747)和禽细胞核磷蛋白B23.1基因序列(NM205267),设计、合成扩增M基因和B23.1基因的引物,利用RT-PCR扩增出M基因和DF1细胞的B23.1基因,分别克隆至真核表达载体获得重组表达质粒pEGFP-M、pCMV-HA-M和pDsRed-B23.1;将pEGFP-M和pDsRed-B23.1共转染HEK-293T细胞,利用荧光显微镜观察M蛋白与B23.1蛋白的共定位;利用免疫共沉淀(Co-IP)技术进一步验证两种蛋白的相互作用。【结果】Western blot结果表明构建的重组质粒在转染的HEK-293T细胞中正确表达;荧光显微镜观察显示M蛋白与B23.1蛋白在核仁具有共定位特征;Co-IP进一步证实两者能发生相互作用。【结论】NDV M蛋白与禽细胞核磷蛋白B23.1存在相互作用,M蛋白可能通过与B23.1蛋白的相互作用进入核仁。 相似文献
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Shijin Tang Yinping Pan Deshuai Lou Shunlin Ji Liancai Zhu Jun Tan Na Qi Qiong Yang Zhi Zhang Biling Yang Wenyan Zhao Bochu Wang 《Protein science : a publication of the Protein Society》2019,28(5):910-919
7α‐Hydroxysteroid dehydrogenase (7α‐HSDH) is an NAD(P)H‐dependent oxidoreductase belonging to the short‐chain dehydrogenases/reductases. In vitro, 7α‐HSDH is involved in the efficient biotransformation of taurochenodeoxycholic acid (TCDCA) to tauroursodeoxycholic acid (TUDCA). In this study, a gene encoding novel 7α‐HSDH (named as St‐2‐1) from fecal samples of black bear was cloned and heterologously expressed in Escherichia coli. The protein has subunits of 28.3 kDa and a native size of 56.6 kDa, which suggested a homodimer. We studied the relevant properties of the enzyme, including the optimum pH, optimum temperature, thermal stability, activators, and inhibitors. Interestingly, the data showed that St‐2‐1 differs from the 7α‐HSDHs reported in the literature, as it functions under acidic conditions. The enzyme displayed its optimal activity at pH 5.5 (TCDCA). The acidophilic nature of 7α‐HSDH expands its application environment and the natural enzyme bank of HSDHs, providing a promising candidate enzyme for the biosynthesis of TUDCA or other related chemical entities. 相似文献
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新城疫(ND)是鸡新城疫强毒株引起的一种鸡的烈性传染病,目前疫苗接种是防治该病的主要手段。临床上曾分离到与中等毒力疫苗株Mukteswar高度同源的强毒株JS/7/05/Ch,其通过静脉注射后毒力显著增强。为了探究JS/7/05/Ch经血液途径毒力增强的机制,本研究选用鸡外周血单个核细胞(PBMC)作为研究模型,分析基因Ⅲ型NDV在PBMC中的靶细胞。细胞分选结果表明病毒感染可诱导PBMC中单核细胞的增殖。实验组病毒感染后单核细胞相对占比上升,感染后1d Mukteswar组(Muk组)单核细胞占比16.3%,JS/7/05/Ch组(JS组)为13.21%,而对照组单核细胞仅占比3.18%。荧光定量PCR测定分选后各细胞中的病毒载量,感染后3d JS组单核细胞中的病毒含量与感染后1d相比极显著性增加(P<0.01)。感染后1d病毒以感染淋巴细胞为主,而在感染后3d单核细胞的相对病毒含量均超过淋巴细胞占据主导地位,Muk组和JS组分别为54.2%和60.2%。综上所述,基因Ⅲ型NDV在PBMC中的靶细胞是单核巨噬细胞。这为进一步研究这对基因Ⅲ型模式病毒毒力差异的机制奠定了一定基础。 相似文献
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Rodriguez-Agudo D Ren S Hylemon PB Redford K Natarajan R Del Castillo A Gil G Pandak WM 《Journal of lipid research》2005,46(8):1615-1623
Recently identified StarD5 belongs to the StarD4 subfamily, a subfamily of steroidogenic acute regulatory related lipid transfer (START) domain proteins that includes StarD4 and StarD6, proteins whose functions remain unknown. The objective of this study was to confirm StarD5's protein localization and sterol binding capabilities as measures to pursue function. Using rabbit polyclonal antibody against newly purified human histidine-tagged/StarD5 protein, StarD5 was detected in human liver. In parallel studies, increased expression of StarD5 in primary hepatocytes led to a marked increase in microsomal free cholesterol. Cell fractionation studies demonstrated StarD5 protein in liver cytosolic fractions only, suggesting StarD5 as a directional cytosolic sterol carrier. Supportive in vitro binding assays demonstrated a concentration-dependent binding of cholesterol by StarD5 similar to that of the cholesterol binding START domain protein StarD1. In contrast to selective cholesterol binding by StarD1, StarD5 bound the potent regulatory oxysterol, 25-hydroxycholesterol, in a concentration-dependent manner. StarD5 binding appeared selective for cholesterol and 25-hydroxycholesterol, as no binding was observed for other tested sterols. The ability of StarD5 to bind not only cholesterol but also 25-hydroxycholesterol, a potent inflammatory mediator and regulatory oxysterol, raises basic fundamental questions about StarD5's role in the maintenance of cellular cholesterol homeostasis. 相似文献