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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >The roles of intrinsic disorder in orchestrating the wnt-pathway.
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The roles of intrinsic disorder in orchestrating the wnt-pathway.

机译：内在障碍在协调wnt途径中的作用。

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The canonical Wnt-pathway plays a number of crucial roles in the development of organism. Malfunctions of this pathway lead to various diseases including cancer. In the inactivated state, this pathway involves five proteins, Axin, CKI-α, GSK-3β, APC, and β-catenin. We analyzed these proteins by a number of computational tools, such as PONDR(r)VLXT, PONDR(r)VSL2, MoRF-II predictor and Hydrophobic Cluster Analysis (HCA) to show that each of the Wnt-pathway proteins contains several intrinsically disordered regions. Based on a comprehensive analysis of published data we conclude that these disordered regions facilitate protein-protein interactions, post-translational modifications, and signaling. The scaffold protein Axin and another large protein, APC, act as flexible concentrators in gathering together all other proteins involved in the Wnt-pathway, emphasizing the role of intrinsically disordered regions in orchestrating the complex protein-protein interactions. We further explore the intricate roles of highly disordered APC in regulation of β-catenin function. Intrinsically disordered APC helps the collection of β-catenin from cytoplasm, facilitates the b-catenin delivery to the binding sites on Axin, and controls the final detachment of β-catenin from Axin.
机译：经典的Wnt途径在生物体的发育中起着至关重要的作用。该途径的功能障碍导致各种疾病，包括癌症。在失活状态下，该途径涉及五种蛋白，即Axin，CKI-α，GSK-3β，APC和β-catenin。我们通过多种计算工具对这些蛋白质进行了分析，例如PONDR（r）VLXT，PONDR（r）VSL2，MoRF-II预测因子和疏水性聚类分析（HCA），以表明每种Wnt途径蛋白均包含几种内在无序的蛋白地区。基于对已发表数据的全面分析，我们得出结论，这些无序区域促进了蛋白质-蛋白质相互作用，翻译后修饰和信号传导。支架蛋白Axin和另一种大蛋白APC在将所有其他参与Wnt途径的蛋白聚集在一起时充当灵活的浓缩剂，强调内在无序区在协调复杂的蛋白-蛋白相互作用中的作用。我们进一步探讨了高度失调的APC在调节β-catenin功能方面的复杂作用。本质上无序的APC有助于从细胞质中收集β-catenin，促进b-catenin传递至Axin的结合位点，并控制β-catenin从Axin的最终脱离。

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