人类Cornulin蛋白S100结构域钙依赖的多聚化能有效减少细胞的损伤(英文)  

The Ca^(2+)-Dependent Multimerization of S100 Domain in Homo sapiens Cornulin Protects Cells From Injury

作　　者：李国明[1,2] 陈强[3,2] 戴克胜[1] 郑晓峰[3,2] 

机构地区：[1]北京航空航天大学生物与医学工程学院,北京100191 [2]北京大学生命科学院生物化学与分子生物学系,北京100871 [3]北京大学植物基因与蛋白质工程国家重点实验室,北京100871

出　　处：《生物化学与生物物理进展》2011年第3期239-247,共9页Progress In Biochemistry and Biophysics

基　　金：supported by grants from National Basic Research Program of China(2007CB914303,2010CB911800);Hi-Tech Research and Development Program of China(2006AA02A314);International Centre for Genetic Engineering and Biotechnology(ICGEB)(CRP/CHN09-01)~~

摘　　要：在哺乳动物中发现一类新的能够抵制环境压力和保持组织完整性的应激蛋白.含有S100钙结合结构域的Cornulin(CRNN)是这类蛋白质之一,它在人类食管鳞状上皮细胞中高表达,而在食管鳞状上皮细胞癌中却低表达,它能抑制脱氧胆酸诱导的细胞损伤.S100结构域在CRNN的功能上具有重要作用.为了进一步探讨CRNN S100结构域的生物学特性,克隆、表达、纯化了该结构域,证明其折叠正确,适合用于生物物理和生物化学特性的研究.更为重要的是,通过核磁共振、凝胶过滤层析、超速离心、质谱和蛋白质交联分析,发现S100结构域具有钙依赖的多聚性质,而多聚体的形成更有利于保护细胞免受脱氧胆酸和乙醇的损伤.上述结果表明,S100结构域是CRNN发挥功能的关键结构域,它可以通过多聚化更好地保护细胞.该工作将进一步揭示S100结构域的生物学功能.A novel type of stress proteins has been identified in mammals to defend environmental stresses and maintain tissue integrity. Cornulin （CRNN） that contains S100 EF-hand Ca^2＋-binding motif is a stress protein highly expressed in the human esophageal squamous epithelial cells. It is downregulated in esophageal sqttamous cell carcinoma and functions as a modifier of deoxycbolic acid （DCA） mediated cell injury. The S100 domain may be central to the function of CRNN. To further characterize the S100 domain of CRNN, the S100 domain in Escheriehia coli, was cloned, expressed, purified and demonstrated that it was properly folded and suitable for biochemical and biophysical studies. More importantly, by nuclear magnetic resonance, gel-filtration, analytical ultracentrifugation, electrospray ionization-mass spectrometry, and Cross-linking analyses, a Ca^2＋-dependent multimeric property of S100 domain was identified. Furthermore, in response to DCA and ethanol challenge, the multimers have stronger protective effects on cells than dimers do. These data indicate that the S100 domain is a key domain in CRNN, which functions as a survival factor through multimerization. This work helps to further understand the feature of S100 domain and its association with cell injury.

关 键 词：Cornulin(CRNN) S100结构域 钙 多聚性质 脱氧胆酸 细胞存活 

分 类 号：Q2[生物学—细胞生物学] Q5