Evidence for the concerted evolution between short linear protein motifs and their flanking regions.
Evidence for the concerted evolution between short linear protein motifs and their flanking regions.
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DOI：
10.1371/journal.pone.0006052
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发表时间：
2009-07-08
期刊：
影响因子：
3.7
通讯作者：
Gibson TJ
中科院分区：
文献类型：
--
作者：
Chica C;Diella F;Gibson TJ
线性基序是蛋白质序列的短模块，在介导和调节许多蛋白质-蛋白质相互作用中起着至关重要的作用。线性基元的功能很大程度上依赖于上下文，例如，功能实例主要发生在可交互访问的灵活区域内。有时，线性基序在多个序列比对中表现为孤立的守恒岛。然而，它们也出现在较大的序列保护块中，这表明邻近的氨基酸起着积极的作用。研究了116个功能线性基序实例侧翼区域的演化。这些区域的氨基酸序列的保守性和有序/无序倾向与实例的存在与否有关。对于大多数分析实例，与缺少线性基序的序列对相比，保留线性基序的序列对也观察到保持相似的局部结构倾向和/或具有更高的局部序列保守性。此外，与距离较远的残基相比，这些实例有更高的机会与邻近残基共同进化。这些发现得到了一些例子的支持，其中线性基序介导的相互作用的调节已被证明依赖于邻近位置的修饰（例如磷酸化），或者被认为受益于无序区域的结合多功能性。结果表明，在结构和序列水平上，侧翼区域与线性基序介导的相互作用有关。更有趣的是，他们指出线性基序实例的预测可以通过执行类似于这里提出的序列分析来丰富上下文信息。这有助于理解这些预测实例在确定它们出现的细胞网络更广泛背景下的蛋白质功能方面的作用。
Linear motifs are short modules of protein sequences that play a crucial role in mediating and regulating many protein–protein interactions. The function of linear motifs strongly depends on the context, e.g. functional instances mainly occur inside flexible regions that are accessible for interaction. Sometimes linear motifs appear as isolated islands of conservation in multiple sequence alignments. However, they also occur in larger blocks of sequence conservation, suggesting an active role for the neighbouring amino acids. The evolution of regions flanking 116 functional linear motif instances was studied. The conservation of the amino acid sequence and order/disorder tendency of those regions was related to presence/absence of the instance. For the majority of the analysed instances, the pairs of sequences conserving the linear motif were also observed to maintain a similar local structural tendency and/or to have higher local sequence conservation when compared to pairs of sequences where one is missing the linear motif. Furthermore, those instances have a higher chance to co–evolve with the neighbouring residues in comparison to the distant ones. Those findings are supported by examples where the regulation of the linear motif–mediated interaction has been shown to depend on the modifications (e.g. phosphorylation) at neighbouring positions or is thought to benefit from the binding versatility of disordered regions. The results suggest that flanking regions are relevant for linear motif–mediated interactions, both at the structural and sequence level. More interestingly, they indicate that the prediction of linear motif instances can be enriched with contextual information by performing a sequence analysis similar to the one presented here. This can facilitate the understanding of the role of these predicted instances in determining the protein function inside the broader context of the cellular network where they arise.
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