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The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle 总被引:4,自引:0,他引:4
Briknarová K Nasertorabi F Havert ML Eggleston E Hoyt DW Li C Olson AJ Vuori K Ely KR 《The Journal of biological chemistry》2005,280(23):21908-21914
p130(cas) (Crk-associated substrate) is a docking protein that is involved in assembly of focal adhesions and concomitant cellular signaling. It plays a role in physiological regulation of cell adhesion, migration, survival, and proliferation, as well as in oncogenic transformation. The molecule consists of multiple protein-protein interaction motifs, including a serine-rich region that is positioned between Crk and Src-binding sites. This study reports the first structure of a functional domain of Cas. The solution structure of the serine-rich region has been determined by NMR spectroscopy, demonstrating that this is a stable domain that folds as a four-helix bundle, a protein-interaction motif. The serine-rich region bears strong structural similarity to four-helix bundles found in other adhesion components like focal adhesion kinase, alpha-catenin, or vinculin. Potential sites for phosphorylation and interaction with the 14-3-3 family of cellular regulators are identified in the domain and characterized by site-directed mutagenesis and binding assays. Mapping the degree of amino acid conservation onto the molecular surface reveals a patch of invariant residues near the C terminus of the bundle, which may represent a previously unidentified site for protein interaction. 相似文献
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Zongmeng Zhang Jie Chen Fanghui Chen Daolun Yu Rui Li Chenglong Lv Haosen Wang Honglin Li Jun Li Yafei Cai 《Cell stress & chaperones》2018,23(4):551-560
Spinal cord injury (SCI) is generally divided into primary and secondary injuries, and apoptosis is an important event of the secondary injury. As an endogenous bile acid and recognized endoplasmic reticulum (ER) stress inhibitor, tauroursodeoxycholic acid (TUDCA) administration has been reported to have a potentially therapeutic effect on neurodegenerative diseases, but its real mechanism is still unclear. In this study, we evaluated whether TUDCA could alleviate traumatic damage of the spinal cord and improve locomotion function in a mouse model of SCI. Traumatic SCI mice were intraperitoneally injected with TUDCA, and the effects were evaluated based on motor function assessment, histopathology, apoptosis detection, qRT-PCR, and western blot at different time periods. TUDCA administration can improve motor function and reduce secondary injury and lesion area after SCI. Furthermore, the apoptotic ratios were significantly reduced; Grp78, Erdj4, and CHOP were attenuated by the treatment. Unexpectedly, the levels of CIBZ, a novel therapeutic target for SCI, were specifically up-regulated. Taken together, it is suggested that TUDCA effectively suppressed ER stress through targeted up-regulation of CIBZ. This study also provides a new strategy for relieving secondary damage by inhibiting apoptosis in the early treatment of spinal cord injury. 相似文献
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Continuum methods are not accurate enough for flows at high Knudsen numbers, whereas rigorous molecular dynamics (MD) methods are too costly for simulations at practical dimensions. Hard-sphere (HS) model is a simplified MD method efficient for dilute gaseous flow but is of poor parallelism due to its event-driven nature, which sets a strong limitation to its large-scale applications. In this work, pseudo-particle modelling, a time-driven modelling approach is coupled with HS model to construct a scalable parallel method capable of simulating flows and transport processes at high Knudsen numbers without losing necessary molecular details in describing their macro-scale behaviours. The method is validated in several classical simulation cases and its performance is evaluated to be favourable. To demonstrate the potential applications of this method, we also simulate the diffusion of small molecules in multi-scale porous media which is related to catalysis, material preparation and micro chemical engineering in the long term. 相似文献
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1988-2013年重庆市主城九区生态用地空间结构及其生态系统服务价值变化 总被引:9,自引:0,他引:9
在当前快速城市化的背景下,理解和把握城市生态系统服务功能退化原因及规律的最有效手段是对其生态用地结构及其生态系统服务价值进行准确的评估。采用RS、GIS技术以及生态系统服务价值评估等方法,对重庆市主城九区1988、1996、2004、2013年4个时段遥感影像进行解译及比较分析,结果表明:1988-2013年间,重庆市主城九区城市化水平经历了加速阶段、减速阶段及饱和阶段,城市化水平的提高对城市建设用地增长的影响显著;重庆市主城九区生态用地主要为城市提供了食物生产、提供原材料、废物处理、土壤形成与保护、气候调节、气体调节、生物多样性以及水源涵养等生态系统服务,在结构变化上呈现出“二减三增”的结构变化特点;25年间重庆市主城九区共减少生态系统服务价值260.60×106元,整体处于下降趋势,其中农地的生态系统服务价值损失最大,共减少24.50%;在空间分布上,随着城市建设用地向“南-北-西”方向扩展,生态系统服务价值以中梁山与铜锣山之间的区域减少最为严重,整个研究区生态系统服务价值下降的主要原因来自于农地的大量减少以及城市建设用地扩张所带来的生态负影响。研究结果表明在重庆市主城九区生态用地空间格局与生态系统服务变化之间存在密切相关性,在城市化率达到饱和阶段后应严格控制建设用地增长,促进建设用地集约节约利用,加大农地的保护力度以及对林地、水体、草地的维护,维持整个区域的生态平衡。研究可为科学合理布局和保护城市生态用地提供信息资料和决策参考。 相似文献
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基于最小累积阻力模型的东北地区生态安全格局构建 总被引:6,自引:0,他引:6
生态安全格局对于缓解生态保护与经济发展之间的矛盾具有积极意义。以东北地区为研究对象,综合参考《生态保护红线划定技术指南》、《全国生态功能区划》以及东北地区自然资源禀赋和社会经济发展水平,基于水源涵养、防风固沙、生物多样性维持与保护等功能指标和敏感性指标划分生态源地;利用夜间灯光数据修正基本生态阻力面,并运用最小累积阻力模型划分缓冲区、识别生态廊道和生态战略节点,从而构建东北地区生态安全格局。结果表明:东北地区生态源地总面积为6.50×105km2,占全区土地总面积的45.02%,包括18个生态源地,主要分布在大兴安岭、小兴安岭、长白山脉和西部草原的部分区域;划分了高、中、低3个水平缓冲区,关键生态廊道中心线总长11073.52km,生态战略节点29个,在东北地区形成以生态源地为中心的网状空间布局。结果可为保障区域生态系统服务功能和可持续发展政策的制定提供科学参考。 相似文献
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Xuejiao Liu Chenglong Yue Lin Shi Guanzheng Liu Qiyu Cao Qianqian Shan Yifeng Wang Xiangyu Chen Huan Li Jie Wang Shangfeng Gao Mingshan Niu Rutong Yu 《Journal of cellular and molecular medicine》2020,24(13):7550-7562
Glioblastoma multiforme (GBM) is the most common malignant tumour in the adult brain and hard to treat. Nuclear factor κB (NF‐κB) signalling has a crucial role in the tumorigenesis of GBM. EGFR signalling is an important driver of NF‐κB activation in GBM; however, the correlation between EGFR and the NF‐κB pathway remains unclear. In this study, we investigated the role of mucosa‐associated lymphoma antigen 1 (MALT1) in glioma progression and evaluated the anti‐tumour activity and effectiveness of MI‐2, a MALT1 inhibitor in a pre‐clinical GBM model. We identified a paracaspase MALT1 that is involved in EGFR‐induced NF‐kB activation in GBM. MALT1 deficiency or inhibition significantly affected the proliferation, survival, migration and invasion of GBM cells both in vitro and in vivo. Moreover, MALT1 inhibition caused G1 cell cycle arrest by regulating multiple cell cycle–associated proteins. Mechanistically, MALTI inhibition blocks the degradation of IκBα and prevents the nuclear accumulation of the NF‐κB p65 subunit in GBM cells. This study found that MALT1, a key signal transduction cascade, can mediate EGFR‐induced NF‐kB activation in GBM and may be potentially used as a novel therapeutic target for GBM. 相似文献
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