Molecular principles of the interactions of disordered proteins
Molecular principles of the interactions of disordered proteins
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DOI：
10.1016/j.jmb.2007.07.004
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发表时间：
2007-09-14
影响因子：
5.6
通讯作者：
Dosztanyi, Zsuzsanna
中科院分区：
文献类型：
--
作者：
Meszaros, Balint;Tompa, Peter;Dosztanyi, Zsuzsanna
深入了解蛋白质-蛋白质识别的分子原理对于我们在细胞水平上理解蛋白质功能至关重要。虽然有序蛋白质的相互作用已被详细分析，但本质上非结构化/无序蛋白质（IUPs）的复合物迄今为止几乎没有得到解决。在这里，我们已经收集了39复合物的实验验证的IUP的数据库，并比较它们的接口与72复合物的有序，球状蛋白质。在两种类型的复合物之间发现的特征差异表明，IUP代表蛋白质-蛋白质识别原理的不同分子实现。接口没有不同的大小，但那些IUPs覆盖了更大的一部分的蛋白质的表面比他们的有序的同行。此外，IUP界面相对于其总体氨基酸组成显著更疏水，但在绝对值上也是如此。它们更多地依赖于疏水-疏水相互作用，而不是极性-极性相互作用。它们在界面中的氨基酸实现了更多的分子间接触，这表明由于在结合时诱导折叠而与伴侣更好地配合，从而导致对伴侣的更好适应。这两种相互作用模式的不同之处还在于，IUP通常仅使用单个连续片段进行伴侣结合，而有序蛋白质的结合位点则更加分段。可能，所有这些功能有助于增加IUP接口残基的进化保守性。这些注意到的分子差异也表现在IUP的相互作用能中。我们通过低分辨率力场对这些进行的近似表明，IUP从分子间接触中获得的稳定能量比从折叠中获得的稳定能量多得多，即它们使用它们的结合能进行折叠。总的来说，我们的研究结果提供了一个结构上的理由，以前的建议，许多宫内节育器是专门为蛋白质-蛋白质相互作用实现的功能。(C)2007爱思唯尔有限公司版权所有。
Thorough knowledge of the molecular principles of protein-protein recognition is essential to our understanding of protein function at the cellular level. Whereas interactions of ordered proteins have been analyzed in great detail, complexes of intrinsically unstructured /disordered proteins (IUPs) have hardly been addressed so far. Here, we have collected a database of 39 complexes of experimentally verified IUPs, and compared their interfaces with those of 72 complexes of ordered, globular proteins. The characteristic differences found between the two types of complexes suggest that lUPs represent a distinct molecular implementation of the principles of protein-protein recognition. The interfaces do not differ in size, but those of IUPs cover a much larger part of the surface of the protein than for their ordered counterparts. Moreover, IUP interfaces are significantly more hydrophobic relative to their overall amino acid composition, but also in absolute terms. They rely more on hydrophobic-hydrophobic than on polar-polar interactions. Their amino acids in the interface realize more intermolecular contacts, which suggests a better fit with the partner due to induced folding upon binding that results in a better adaptation to the partner. The two modes of interaction also differ in that IUPs usually use only a single continuous segment for partner binding, whereas the binding sites of ordered proteins are more segmented. Probably, all these features contribute to the increased evolutionary conservation of IUP interface residues. These noted molecular differences are also manifested in the interaction energies of lUPs. Our approximation of these by low-resolution force-fields shows that lUPs gain much more stabilization energy from intermolecular contacts, than from folding, i.e. they use their binding energy for folding. Overall, our findings provide a structural rationale to the prior suggestions that many IUPs are specialized for functions realized by protein-protein interactions. (C) 2007 Elsevier Ltd. All rights reserved.