DYNAMIC ASSEMBLY OF PROTEIN COMPLEXES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 26 S蛋白酶体是存在于所有真核生物中的大分子机器，负责细胞质和细胞核中的泛素/ATP依赖的蛋白质降解。它由两个亚复合物组成，20 S核心颗粒（CP）和19 S调节复合物（RP）。20 S CP负责各种催化活性，而19 S RP参与几种生化功能，包括识别和解折叠多泛素化底物，帮助打开20 S室的门，随后将解折叠的底物转移到20 S中进行降解。细胞内的选择性降解受到严格控制，在调节细胞周期进程、信号转导和维持基因组稳定等方面起着重要作用。正常蛋白水解破坏途径的破坏可导致广泛的人类疾病，包括癌症和神经退行性疾病。 尽管进行了深入的研究，未知的仍然超过了目前已知的泛素/蛋白酶体依赖性降解。为了了解26 S蛋白酶体功能的调节，我们有兴趣研究在不同的生理条件下26 S蛋白酶体复合物的动态结构变化。

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.