Attributes of short linear motifs
Attributes of short linear motifs
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DOI：
10.1039/c1mb05231d
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Gibson, Toby J.
中科院分区：
文献类型：
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作者：
Davey, Norman E.;Van Roey, Kim;Gibson, Toby J.
传统上，蛋白质之间的相互作用被认为是由大的、结构化的结构域所介导的。然而，很明显，相互作用体包括广泛的结合界面，具有不同程度的灵活性，从刚性的球状结构域到天生缺乏结构的无序区域。高度连接的中枢蛋白中对无序的富集性及其与生物体复杂性的相关性暗示了无序区域的功能重要性。然而，它们还没有被广泛地描述出来。将注意力从球状结构域转移到蛋白质组的无序区域可能会使我们更接近于阐明相互作用组的密集和复杂的连接。一类重要的无序界面是紧凑的单组分短线状基序(SLIMs，或真核线型基序(ELM))。它们在进化上是可塑性的，由于与结合伙伴直接接触的残基数量有限，它们相互作用的亲和力相对较低。这些特征赋予瘦身能力，使其能够收敛地演进和调节瞬时交互，这对于网络演进和保持强大的小区信令分别是必不可少的。通过不同的属性区分与生物相关的苗条的能力将提高我们对相互作用组的复杂性的理解，并有助于开发用于发现基序的生物信息学工具。在这篇文章中，分析了目前在真核生物线性基序(ELM)数据库中可用的精选实例，以提供对SLIM的定义属性的清晰概述。这些分析表明，功能苗条比其周围残基具有更高的保守性，经常收敛进化，优先出现在无序区域，并在与其相互作用伙伴结合时经常形成二级结构。这些结果主张在相对保守性较高和有形成二级结构倾向的无序区域中寻找小残基。最后，就其功能后果对最有趣的结论进行了检验。
Traditionally, protein-protein interactions were thought to be mediated by large, structured domains. However, it has become clear that the interactome comprises a wide range of binding interfaces with varying degrees of flexibility, ranging from rigid globular domains to disordered regions that natively lack structure. Enrichment for disorder in highly connected hub proteins and its correlation with organism complexity hint at the functional importance of disordered regions. Nevertheless, they have not yet been extensively characterised. Shifting the attention from globular domains to disordered regions of the proteome might bring us closer to elucidating the dense and complex connectivity of the interactome. An important class of disordered interfaces are the compact mono-partite, short linear motifs (SLiMs, or eukaryotic linear motifs (ELMs)). They are evolutionarily plastic and interact with relatively low affinity due to the limited number of residues that make direct contact with the binding partner. These features confer to SLiMs the ability to evolve convergently and mediate transient interactions, which is imperative to network evolution and to maintain robust cell signalling, respectively. The ability to discriminate biologically relevant SLiMs by means of different attributes will improve our understanding of the complexity of the interactome and aid development of bioinformatics tools for motif discovery. In this paper, the curated instances currently available in the Eukaryotic Linear Motif (ELM) database are analysed to provide a clear overview of the defining attributes of SLiMs. These analyses suggest that functional SLiMs have higher levels of conservation than their surrounding residues, frequently evolve convergently, preferentially occur in disordered regions and often form a secondary structure when bound to their interaction partner. These results advocate searching for small groupings of residues in disordered regions with higher relative conservation and a propensity to form the secondary structure. Finally, the most interesting conclusions are examined in regard to their functional consequences.