PROTEASOME (26S PROTEASOME)

蛋白酶体（26S 蛋白酶体）

• 批准号: 8168596
• 负责人: George N. DeMartino
• 金额: $ 1.08万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168596
• 关键词: 26S proteasome; Amino Acids; Apoptosis; Archaea; Bacteria; Cattle; Cell Cycle Regulation; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA Repair; Degradation Pathway; Eukaryota; Funding; Grant; Institution; Peptides; Process; Proteins; Quality Control; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Signal Transduction; Solutions; Source; Structure; Ubiquitin; United States National Institutes of Health; multicatalytic endopeptidase complex; particle; protein complex; protein misfolding; 26S proteasome; Amino Acids; Apoptosis; Archaea; Bacteria; Cattle; Cell Cycle Regulation; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA Repair; Degradation Pathway; Eukaryota; Funding; Grant; Institution; Peptides; Process; Proteins; Quality Control; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Signal Transduction; Solutions; Source; Structure; Ubiquitin; United States National Institutes of Health; multicatalytic endopeptidase complex; particle; protein complex; protein misfolding

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. Proteasomes are large dynamic protein complexes existing inside all eukaryotes and archaea, as well as in some bacteria. The major function of the proteasome is to degrade misfolded or damaged proteins by breaking peptide bonds in an ATP-dependent manner. The polymerized ubiquitin chain acts as a degradation signal that carries the target proteins to the proteasome, where the substrate is proteolytically broken down. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. The degradation process yields peptides of about seven to eight amino acids long, which can then be further degraded into amino acids and used in synthesizing new proteins. The ubiquitin-proteasome degradation pathway is essential for many cellular processes, including cell-cycle regulation, DNA repair, apoptosis, signal transduction, and protein quality control. We are going to examine the structures of Bovine 26S proteasomes by single-particle cryo-EM. The specific aims for this proposal are: 1) to solve and compare the structures of single-capped 26S proteasome and double-capped 30S proteasome at subnanometer resolution; 2) to compare the solution structure of non-capped 20S by cryo-EM with the X-ray structure of 20S; 3) to further elucidate the gate opening mechanism of the 26S proteasome by comparing the cryo-EM structures of 26S and 30S with the known structure(s) of 20S, in which the gate in ¿¿ ring(s) remains closed to block the free entry of even unfolded substrates.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 蛋白酶体是所有真核生物和古细菌以及某些细菌中存在的大型动态蛋白质复合物。蛋白质组的主要功能是通过以ATP依赖性方式破坏胡椒键来降解错误折叠或受损的蛋白质。聚合的泛素链充当降解信号，该信号将靶蛋白带到蛋白酶体，底物被蛋白水解分解。蛋白酶体是细胞调节特定蛋白质浓度和降解错误折叠蛋白的主要机制的一部分。降解过程的长度约为七至八个氨基酸，然后可以进一步降解为氨基酸，并用于合成新蛋白质。泛素 - 凝血素降解途径对于许多细胞过程至关重要，包括细胞周期调节，DNA修复，凋亡，信号转导和蛋白质质量控​​制。 我们将通过单粒子冷冻EM检查牛26S蛋白酶体的结构。该提案的具体目的是：1）在亚纳光分辨率下解决和比较单封的26S蛋白酶体和双封型30S蛋白酶体的结构； 2）比较Cryo-Em的非封闭20S的溶液结构与20S的X射线结构； 3）通过将26s和30s的冷冻EM结构与已知结构（s）的20S结构进行比较，在``````s）中''的栅极结构进行了比较，从而进一步阐明了26S蛋白酶体的栅极开口机理，其中````s）''环（S）中的栅极保持封闭以阻止自由进入展开的底物。