The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains.
The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains.
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肌联蛋白的弹性 I 带区域通过弱相互作用的 Ig 样结构域以“模块化”方式组装。
DOI：
10.1006/jmbi.1996.0050
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发表时间：
1996
影响因子：
5.6
通讯作者：
A. Pastore
中科院分区：
文献类型：
--
作者：
A. Politou;M. Gautel;S. Improta;L. Vangelista;A. Pastore
脊椎动物横纹肌肌联蛋白被认为在肌原纤维组装和被动张力中起关键作用。最近确定的完整的一级结构的肌联蛋白揭示了一个模块化的架构，打开了一个结构表征和理解的基本性质，这个分子通过解剖成单位，结构和/或功能相关。为了了解肌联蛋白的组装过程，并最终了解其弹性行为的分子基础，我们研究了模块对的热力学性质，模块对是包括模块-模块界面的最小结构单元。因此，选择的模块对和它们的组件的单一模块从I-带部分的肌联蛋白分子在大肠杆菌中表达，其热诱导和变性剂诱导的展开进行了研究与组合的技术（圆二色性，荧光光谱和核磁共振）。通过变性实验确定了单个模块和模块对的稳定性。模块接口也被建模的基础上的所有约40个免疫球蛋白样模块的序列比对的I-带和其中之一的已知结构。我们的结果表明，所有的模块和模块对检查独立折叠的解决方案。当共价连接时，尽管相互作用很弱，但它们在展开时仍然表现为自主合作单位。这些观察结果使我们认为，在体外折叠的肌联蛋白是一个层次的事件，其相邻模块之间的弱相互作用必须只部分占其假定的弹性功能。
The vertebrate striated muscle protein titin is thought to play a critical rôle in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all approximately 40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.