PROTEASOME (26S PROTEASOME)

蛋白酶体（26S 蛋白酶体）

• 批准号: 8361104
• 负责人: George N. DeMartino
• 金额: $ 1.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361104
• 关键词: 26S proteasome; Amino Acids; Apoptosis; Archaea; Bacteria; Cattle; Cell Cycle Regulation; Cell physiology; Cells; DNA Repair; Degradation Pathway; Electron Microscopy; Eukaryota; Funding; Grant; National Center for Research Resources; Peptides; Principal Investigator; Process; Proteins; Quality Control; Research; Research Infrastructure; Resolution; Resources; Roentgen Rays; Signal Transduction; Solutions; Source; Structure; Ubiquitin; United States National Institutes of Health; cost; macromolecule; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 蛋白酶体是存在于所有真核生物和古细菌内部的大型动态蛋白质复合物， 以及在某些细菌中，蛋白酶体的主要功能是降解错误折叠或错误折叠的蛋白质。 通过以 ATP 依赖性方式破坏肽键来破坏蛋白质。 泛素链充当降解信号，将目标蛋白携带至 蛋白酶体，其中底物被蛋白水解分解，蛋白酶体是蛋白酶体的一部分。 细胞调节特定蛋白质浓度的主要机制 降解错误折叠的蛋白质 降解过程产生大约七到八个肽。 氨基酸长，然后可以进一步降解为氨基酸并用于 泛素-蛋白酶体降解途径对于合成新蛋白质至关重要。 许多细胞过程，包括细胞周期调节、DNA 修复、细胞凋亡、信号 转导和蛋白质质量控​​制。 我们将通过单粒子冷冻检查牛 26S 蛋白酶体的结构 EM。该提案的具体目标是：1）解决和比较单结构 亚纳米分辨率的加帽 26S 蛋白酶体和双加帽 30S 蛋白酶体 2) 通过冷冻电镜将非封端 20S 的溶液结构与 X 射线结构进行比较 20S；3)进一步阐明26S蛋白酶体的开门机制 将 26S 和 30S 的冷冻电镜结构与 20S 的已知结构进行比较， 哪个门在 ¿环保持关闭以阻止甚至展开的自由进入 基材。