All repeats are not equal: a module-based approach to guide repeat protein design.
All repeats are not equal: a module-based approach to guide repeat protein design.
复制标题
所有重复并不相同：一种基于模块的方法来指导重复蛋白质设计。
DOI：
10.1016/j.jmb.2013.02.013
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发表时间：
2013
影响因子：
5.6
通讯作者：
Regan,Lynne
中科院分区：
文献类型：
--
作者：
Sawyer,Nicholas;Chen,Jieming;Regan,Lynne
由短结构基序的串联阵列组成的重复蛋白质通常介导蛋白质-蛋白质相互作用。过去设计基于重复蛋白的分子识别工具的努力集中在从单个重复序列的一致性创建模板，而不管它们的自然背景。这种方法假设所有重复基本上是等价的。在这项研究中，我们提出了一个“基于模块”的方法，其中串联重复序列组成的模块对齐，以确定重复特定的功能。使用这种方法来分析含有三个串联重复序列（3 TPR）的tetratricopeptide重复模块，我们确定了两类3 TPR模块与不同的结构特征，与不同的功能残基。我们的分析还揭示了整个配体结合表面的位置之间的高度相关性，表明协调，共同进化的结合表面。我们的分析扩展到不同的重复蛋白模块揭示了更多的重复特定功能的例子，特别是在犰狳重复模块。总之，我们提出的基于模块的分析有效地捕获了关键的重复序列特异性特征，这些特征对于将来的重复序列蛋白质设计模板非常重要。
Repeat proteins composed of tandem arrays of a short structural motif often mediate protein–protein interactions. Past efforts to design repeat protein-based molecular recognition tools have focused on the creation of templates from the consensus of individual repeats, regardless of their natural context. Such an approach assumes that all repeats are essentially equivalent. In this study, we present the results of a “module-based” approach in which modules composed of tandem repeats are aligned to identify repeat-specific features. Using this approach to analyze tetratricopeptide repeat modules that contain three tandem repeats (3TPRs), we identify two classes of 3TPR modules with distinct structural signatures that are correlated with different sets of functional residues. Our analyses also reveal a high degree of correlation between positions across the entire ligand-binding surface, indicative of a coordinated, coevolving binding surface. Extension of our analyses to different repeat protein modules reveals more examples of repeat-specific features, especially in armadillo repeat modules. In summary, the module-based analyses that we present effectively capture key repeat-specific features that will be important to include in future repeat protein design templates.