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首页> 外文期刊>Journal of Molecular Biology >Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions
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Towards Decoding the Sequence-Based Grammar Governing the Functions of Intrinsically Disordered Protein Regions

机译：朝向控制序列的语法治疗内部无序蛋白质区域的功能

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摘要

A substantial portion of the proteome consists of intrinsically disordered regions (IDRs) that do not fold into well-defined 3D structures yet perform numerous biological functions and are associated with a broad range of diseases. It has been a long-standing enigma how different IDRs successfully execute their specific functions. Further putting a spotlight on IDRs are recent discoveries of functionally relevant biomolecular assemblies, which in some cases form through liquid-liquid phase separation. At the molecular level, the formation of biomolecular assemblies is largely driven by weak, multivalent, but selective IDR-IDR interactions. Emerging experimental and computational studies suggest that the primary amino acid sequences of IDRs encode a variety of their interaction behaviors. In this review, we focus on findings and insights that connect sequence-derived features of IDRs to their conformations, propensities to form biomolecular assemblies, selectivity of interaction partners, functions in the context of physiology and disease, and regulation of function. We also discuss directions of future research to facilitate establishing a comprehensive sequence-function paradigm that will eventually allow prediction of selective interactions and specificity of function mediated by IDRs. (C) 2020 Elsevier Ltd. All rights reserved.
机译：蛋白质组的很大一部分由内在无序区域（IDR）组成，这些区域不折叠成明确的3D结构，但具有多种生物学功能，并与广泛的疾病相关。不同的IDR如何成功地执行其特定功能一直是个谜。最近发现的功能相关的生物分子组装体，在某些情况下是通过液-液相分离形成的，这使IDR受到了进一步的关注。在分子水平上，生物分子组装的形成在很大程度上是由弱、多价但选择性的IDR-IDR相互作用驱动的。新兴的实验和计算研究表明，IDR的一级氨基酸序列编码其多种相互作用行为。在这篇综述中，我们着重于发现和见解，这些发现和见解将IDR的序列衍生特征与其构象、形成生物分子组装的倾向、相互作用伙伴的选择性、生理和疾病背景下的功能以及功能调节联系起来。我们还讨论了未来的研究方向，以促进建立一个全面的序列功能范式，最终允许预测IDRs介导的选择性相互作用和功能特异性。（C） 2020爱思唯尔有限公司版权所有。

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