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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 蛋白酶体是所有真核生物和古细菌内部存在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 通过以ATP依赖性方式破坏肽键来损坏蛋白质。聚合 泛素链充当降解信号，将靶蛋白带到 蛋白酶体，底物被蛋白水解分解。蛋白酶体是一个 细胞调节特定蛋白质浓度的主要机制和 降解错误折叠的蛋白质。降解过程产生了大约七到八的宠物 氨基酸长，然后可以将其进一步降解为氨基酸并使用 合成新蛋白质。泛素 - 蛋白酶体降解途径对于 许多细胞过程，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。该提案的具体目的是：1）解决和比较单一的结构 在亚纳米分辨率下，限制了26S蛋白酶体和双封型30S蛋白酶体； 2） 比较Cryo-EM的非封闭20S的溶液结构与X射线结构 20年代; 3）进一步阐明26S蛋白酶体的门打开机理 将26s和30s的冷冻EM结构与已知结构的20s结构进行比较 环中的大门保持闭合，以阻止即使展开的自由进入 基材。