Intrinsic Protein Disorder and Protein-Protein Interactions
Intrinsic Protein Disorder and Protein-Protein Interactions
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DOI：
10.7490/f1000research.1090909.1
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发表时间：
2012-08
影响因子：
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通讯作者：
W. Hsu;C. Oldfield;Jingwei Meng;Fei Huang;B. Xue;V. Uversky;P. Romero;A. Dunker
中科院分区：
文献类型：
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作者：
W. Hsu;C. Oldfield;Jingwei Meng;Fei Huang;B. Xue;V. Uversky;P. Romero;A. Dunker
本质上无序的蛋白质通常会与不止一个伴侣结合。在这项研究中，我们集中在11组复合体中，在这些复合体中，相同的无序片段与两个或更多不同的伙伴结合。对于这组蛋白质复合体，每个无序片段的两个或更多配对被选择为在结构排列的位置具有低于25%的氨基酸同一性。由于大多数这样选择的例子都具有相似的3D结构，所以研究集被简化为仅这些相似折叠的情况。根据相互作用伙伴的分析，伙伴结合区的平均序列同源性比非结合区显示出更高的保守性：11组伙伴蛋白的平均残基同一性如下：结合残基42±6%；非结合残基20±3%；非结合埋藏残基26±5%；非结合表面残基16±3%。与其他残基相比，结合残基的序列同源性更高，这证明这些观察到的相互作用很可能是有意义的生物相互作用，而不是人工制品。由于各种相互作用的许多特征表明，无序的结合片段可能在结合前已经无序，这些结果也进一步增加了细胞内固有无序区域的存在和功能。
Intrinsically disordered proteins often bind to more than one partner. In this study, we focused on 11 sets of complexes in which the same disordered segment becomes bound to two or more distinct partners. For this collection of protein complexes, two or more partners of each disordered segment were selected to have less than 25% amino acid identity at structurally aligned positions. As it turned out that most of the examples so selected had similar 3D structure, the studied set was reduced to just these similar-fold cases. Based on the analyses of the interacting partners, the average sequence identity of the partners' binding regions showed substantially higher conservation as compared to the nonbinding regions: The residue identities, averaged over the 11 sets of partner proteins, were as follows: binding residues, 42 ± 6%; nonbinding residues 20 ± 3%; nonbinding buried residues 26 ± 5%; and nonbinding surface residues 16 ± 3%. The higher sequence identity of the binding residues compared to the other sets of residues provides evidence that these observed interactions are likely to be meaningful biological interactions, not artifacts. Since many of the features of the various interactions indicate that the disordered binding segments were likely to have been disordered before binding, these results also add further weight to the existence and function of intrinsically disordered regions inside cells.