DYNAMIC ASSEMBLY OF PROTEIN COMPLEXES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 26S蛋白酶体是存在于所有真核生物中的一种大分子机器，负责胞浆和胞核中泛素/ATP依赖的蛋白质的降解。它由两个亚复合体组成，即20S核心粒子(CP)和19S调节复合体(RP)。20S CP负责各种催化活性，而19S RP参与多种生化功能，包括识别和打开多泛素底物，帮助打开20S小室的门，随后将未折叠的底物转移到20S进行降解。细胞中的选择性降解受到严格的控制，在调节细胞周期进程、信号转导和维持基因组稳定等方面发挥着重要作用。正常的蛋白分解破坏途径可以导致广泛的人类疾病，包括癌症和神经退行性疾病。尽管进行了大量的研究，但未知的情况仍然超过了目前已知的泛素/蛋白酶体依赖的降解。为了了解26S蛋白酶体功能的调控，我们有兴趣研究不同生理条件下26S蛋白酶体复合体结构的动态变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The 26S proteasome is a macromolecular machine existing in all eukaryotes and is responsible for ubiquitin/ATP dependent protein degradation in both cytosol and nucleus. It consists of two subcomplexes, the 20S core particle (CP) and the 19S regulatory complex (RP). The 20S CP is responsible for various catalytic activities, while the 19S RP is involved in several biochemical functions including recognition and unfolding of polyubiquitinated substrates, assisting in opening the gate of the 20S chamber and subsequently translocating unfolded substrates into the 20S for degradation. Selective degradation in cells is tightly controlled and plays an important role for regulating cell cycle progression, signal transduction and maintaining genome stability, etc. Disruption of normal proteolytic destruction pathways can lead to a wide range of human disease, including cancer and neurodegenerative disorders. Despite intensive research, the unknown still exceeds what are currently known on ubiquitin/proteasome dependent degradation. In order to understand the regulation of the 26S proteasome function, we are interested in studying dynamic structural changes in the 26S proteasome complex under different physiological conditions.