Ump1和β亚单元的结构作用在蛋白质酶生物发生过程中
Eric Mark1, Paula C Ramos2, Fleur Kayser1
1Institute of Biochemistry and Biology, Department of Biochemistry, University of Potsdam, Potsdam-Golm, Germany.
Life science alliance
|September 11, 2024
概括
酵母蛋白酶突变的pre1-1捕获Ump1和Pba1-Pba2在前体复合体中. 化EM揭示了Ump1与的相互作用,详细说明了早期成熟阶段和形状变化.
科学领域:
- * 分子和细胞生物学
- * 结构生物学 * 结构生物学
- * 生物化学 * 生物化学
背景情况:
- *20S蛋白酶体是一个大型蛋白酶复合体,对蛋白质平衡至关重要.
- * 蛋白质体成熟涉及组装和处理子单元,由组装伴侣如Ump1和Pba1-Pba2.2指导.
- * 了解蛋白酶组装中间体对于破译其功能调节至关重要.
研究的目的:
- * 确定酵母前1-1突变体中20S晚期蛋白酶体前体复合物的冷电子显微镜 (cryo-EM) 结构.
- * 为了阐明组合伴侣Ump1和辅助蛋白Pba1-Pba2在这种中间体中的结构相互作用.
- * 了解20S蛋白酶体成熟和子单元处理的早期事件.
主要方法:
- *冷电子显微镜 (cryo-EM) 在2.1 Å分辨率.
- * 酵母蛋白酶体前体复合物的结构分析.
- *子单元相互作用和处理的生物化学特征.
主要成果:
- *获得了20S晚期蛋白酶体前体复合体 (late-PC) 的高分辨率冷EM结构.
- * 结构显示全长的Ump1被困在α环内,与β2-和β5-propeptides密切相互作用.
- *β2亚单元的自催化激活启动了一连串的蛋白处理和复合稳定,导致Ump1降解和Pba1-Pba2释放.
结论:
- *该结构提供了前所未有的细节,说明了控制早期蛋白酶组装和成熟的相互作用.
- * 蛋白质体成熟涉及重要的全球形状变化,由蛋白质溶解部位结构化和自催化激活驱动.
- *酵母前1-1突变体作为一个有价值的模型来研究20S蛋白酶体生物发生的动态过程.
相关概念视频
The Proteasome Structure
718
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
718
The Proteasome
818
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
818
The Unfolded Protein Response
4.5K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
Mitochondrial Precursor Proteins
2.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.5K
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Regulated Protein Degradation
7.2K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.2K


