The role of intrinsic protein disorder in regulation of cyclin-dependent kinases

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in structural biology Pub Date : 2024-08-13 DOI:10.1016/j.sbi.2024.102906
Aaron H. Phillips, Richard W. Kriwacki
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Abstract

While the structure/function paradigm for folded domains was established decades ago, our understanding of how intrinsically disordered regions (IDRs) contribute to biological function is still evolving. IDRs exist as conformational ensembles that can range from highly compact to highly extended depending on their sequence composition. IDR sequences are less conserved than those of folded domains, but often display short, conserved segments termed short linear motifs (SLiMs), that often mediate protein–protein interactions and are often regulated by posttranslational modifications, giving rise to complex functionality when multiple, differently regulated SLiMs are combined. This combinatorial functionality was associated with signaling and regulation soon after IDRs were first recognized as functional elements within proteins. Here, we discuss roles for disorder in proteins that regulate cyclin-dependent kinases, the master timekeepers of the eukaryotic cell cycle. We illustrate the importance of intrinsic flexibility in the transmission of regulatory signals by these entirely disordered proteins.

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内在蛋白质紊乱在周期蛋白依赖性激酶调控中的作用
虽然折叠结构域的结构/功能范式早在几十年前就已确立,但我们对固有无序区(IDR)如何促进生物功能的认识仍在不断发展。IDR以构象组合的形式存在,根据其序列组成,可以从高度紧凑到高度扩展不等。与折叠结构域相比,IDR 序列的保守性较低,但通常显示出短而保守的片段,这些片段被称为短线性母题(SLiMs),通常介导蛋白质与蛋白质之间的相互作用,并经常受到翻译后修饰的调控,当多个不同调控的 SLiMs 组合在一起时,就会产生复杂的功能。在 IDR 首次被认为是蛋白质内的功能元素后不久,这种组合功能就与信号传递和调控联系在了一起。在这里,我们讨论了调节细胞周期蛋白依赖性激酶(真核细胞周期的主要计时者)的蛋白质中的紊乱作用。我们说明了这些完全无序的蛋白质在传递调控信号时内在灵活性的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current opinion in structural biology
Current opinion in structural biology 生物-生化与分子生物学
CiteScore
12.20
自引率
2.90%
发文量
179
审稿时长
6-12 weeks
期刊介绍: Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation
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