The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have carried out the functional intrinsic disorder and MoRF analysis for potential neurodegenerative disease and anti-cancer targets of this pathway. Our report represents the presence of significant intrinsic disorder and disorder-based binding regions in several UPS proteins, such as extraproteasomal polyubiquitin receptors (UBQLN1 and UBQLN2), proteasome-associated polyubiquitin receptors (ADRM1 and PSMD4), deubiquitinating enzymes (DUBs) (ATXN3 and USP14), and ubiquitinating enzymes (E2 (UBE2R2) and E3 (STUB1) enzyme). We believe this study will have implications for the conformation-specific roles of different regions of these proteins. This will lead to a better understanding of the molecular basis of UPS-associated diseases.

中文翻译：

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泛素-蛋白酶体系统蛋白质的非结构化生物学：在癌症和神经退行性疾病中的作用。


26S 蛋白酶体是一种大型 (~2.5 MDa) 蛋白质复合物，由至少 33 个不同的亚基和许多其他组件组成，形成泛素蛋白酶体系统 (UPS)，这是细胞中依赖于 ATP 的蛋白质降解系统。 UPS 是细胞蛋白质监视机制的重要组成部分，其功能障碍会导致癌症、神经退行性和免疫性疾病。重要的是，蛋白质的功能和调控是由有序区域、本质无序蛋白质区域（IDPR）和分子识别特征（MoRF）的组合控制的。 UPS各部件的结构-功能关系尚未完全确定；因此，在本研究中，我们对该通路的潜在神经退行性疾病和抗癌靶点进行了功能性内在障碍和MoRF分析。我们的报告表明，几种 UPS 蛋白中存在显着的内在紊乱和基于紊乱的结合区域，例如蛋白酶体外多聚泛素受体（UBQLN1 和 UBQLN2）、蛋白酶体相关多聚泛素受体（ADRM1 和 PSMD4）、去泛素化酶 (DUB)（ATXN3 和USP14) 和泛素化酶（E2 (UBE2R2) 和 E3 (STUB1) 酶）。我们相信这项研究将对这些蛋白质不同区域的构象特异性作用产生影响。这将有助于更好地了解 UPS 相关疾病的分子基础。