Protein intrinsic disorder is an important characteristic commonly detected in multifunctional or RNA- and DNA-binding proteins. Due to their high conformational flexibility and solvent accessibility, intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) execute diverse functions including interaction with multiple partners, and are frequently subjected to various post-translational modifications. Recent studies on the components comprising the CRISPR (clustered regularly interspaced short palindromic repeats) system have elucidated the crystal structure of Cas9 proteins and the mechanism by which the Cas9–sgRNA complex recognizes and cleaves its target DNA. Yet the extent and functional implications of intrinsic disorder in the Cas9 protein have never been fully assessed. Here, we present a comprehensive computational analysis based on both sequence and structural data in an attempt to investigate the roles of IDPRs in the functioning of Cas9 proteins of different origin. We conclude that among the functional roles of IDPRs in Cas9 proteins are recognition of the target DNA and mediation of nucleic acid and protein binding.

中文翻译：

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内源性疾病在CRISPR相关蛋白Cas9中的功能作用

蛋白质内在障碍是在多功能或RNA和DNA结合蛋白中通常检测到的重要特征。由于它们的高构象柔韧性和溶剂可及性，内在无序的蛋白质（IDPs）和IDP区域（IDPRs）执行各种功能，包括与多个配偶体的相互作用，并经常进行各种翻译后修饰。最近对组成CRISPR（有规律地相互间隔的短回文重复序列）系统的成分的研究阐明了Cas9蛋白质的晶体结构，以及Cas9–sgRNA复合体识别和切割其靶DNA的机制。但是，尚未充分评估Cas9蛋白中内在障碍的程度和功能含义。这里，我们提出了基于序列和结构数据的综合计算分析，以试图研究IDPR在不同来源的Cas9蛋白质的功能中的作用。我们得出结论，Cas9蛋白质中IDPR的功能性作用是对目标DNA的识别以及核酸和蛋白质结合的介导。