Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structures under physiological conditions in vitro. They are highly abundant in nature and their functional repertoire complements the functions of ordered proteins. IDPs are involved in regulation, signaling, and control, where binding to multiple partners and high-specificity/low-affinity interactions play a crucial role. Functions of IDPs are tuned via alternative splicing and posttranslational modifications. Intrinsic disorder is a unique structural feature that enables IDPs to participate in both one-to-many and many-to-one signaling. Numerous IDPs are associated with human diseases, including cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, and diabetes. Overall, intriguing interconnections among intrinsic disorder, cell signaling, and human diseases suggest that protein conformational diseases may result not only from protein misfolding, but also from misidentification, missignaling, and unnatural or nonnative folding. IDPs, such as alpha-synuclein, tau protein, p53, and BRCA1, are attractive targets for drugs modulating protein-protein interactions. From these and other examples, novel strategies for drug discovery based on IDPs have been developed. To summarize work in this area, we are introducing the D2 (disorder in disorders) concept.

中文翻译：

---

人类疾病中的内在无序蛋白：引入D2概念。

本质上无序的蛋白质（IDP）在体外生理条件下缺乏稳定的三级和/或二级结构。它们本质上高度丰富，其功能库可补充有序蛋白质的功能。IDP参与调节，信号传导和控制，其中与多个伙伴的结合以及高特异性/低亲和力相互作用起着至关重要的作用。IDP的功能可通过其他剪接和翻译后修饰进行调整。固有疾病是一种独特的结构特征，使IDP能够参与一对多和多对一的信号传递。许多IDP与人类疾病相关，包括癌症，心血管疾病，淀粉样蛋白，神经退行性疾病和糖尿病。总体而言，内在障碍，细胞信号传导，人类疾病表明，蛋白质构象性疾病不仅可能是由于蛋白质错误折叠引起的，而且还可能是由于错误识别，错误识别以及非自然或非自然折叠引起的。IDP，例如α-突触核蛋白，tau蛋白，p53和BRCA1，是调节蛋白-蛋白相互作用的药物的有吸引力的靶标。从这些和其他示例中，已经开发了基于IDP的新型药物发现策略。为了总结该领域的工作，我们引入了D2（疾病障碍）概念。从这些和其他示例中，已经开发了基于IDP的新型药物发现策略。为了总结该领域的工作，我们引入了D2（疾病障碍）概念。从这些和其他示例中，已经开发了基于IDP的新型药物发现策略。为了总结该领域的工作，我们引入了D2（疾病障碍）概念。