隆慢慢地降解稳定基质,但具有增强的过程性,重新定义了成功的AAA+蛋白酶的属性
Meghann R Kasal1, Hema Chandra Kotamarthi1, Madeline M Johnson2
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell reports
|September 3, 2023
概括
伦蛋白酶 (与各种细胞活动相关的ATPases) 可以展开并降解稳定的蛋白质. 这项研究揭示了它的动力冲击机制和高流动性,这是Lon家族的关键.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 单蛋白酶是与各种细胞活动 (AAA+) 相关的ATPases,这些酶参与蛋白质降解.
- 它们通常被认为是弱解酶,主要降解错误折叠或损坏的蛋白质.
- 伦蛋白酶功能的特定机制,特别是对于稳定折叠的基质,仍然不完全理解.
研究的目的:
- 为了阐明 Mesoplasma florum Lon (MfLon) 蛋白酶的分子机制.
- 研究MfLon在稳定折叠基板上的展开酶和转位能力.
- 将MfLon的机制和过程性与其他AAA+蛋白酶进行比较.
主要方法:
- 组装生物化学分析.
- 单分子生物物理实验.
- 使用来自Mesoplasma florum (MfLon和MfssrA) 的一个Lon-degron对.
主要成果:
- MfLon展示了展开和降解稳定折叠蛋白质基质的能力.
- 多转位发生在约6个氨基酸的离散步骤中.
- ATP 水解与转位紧密结合,一个ATP水解事件为每个转位步骤 (动力冲击) 提供燃料.
- 与ClpXP和ClpAP蛋白酶相比,MfLon的过程性更高.
结论:
- MfLon通过动力冲击机制起作用,与其他HCLR类AAA+酶相一致.
- MfLon的强烈展开酶活性和高过程性有助于Lon蛋白酶家族的进化成功.
- 这些发现扩大了我们对AAA+蛋白酶机制和基质降解途径的理解.
相关概念视频
02:18The Proteasome
8.8K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst 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. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
8.8K
01:17The Proteasome Structure
801
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...
801
01:19Allosteric Proteins-ATCase
5.8K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
02:58Regulated Protein Degradation
7.4K
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...
7.4K
02:34Enzymes
81.8K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
81.8K
01:29Leveling Effect
832
In acid-base chemistry, the leveling effect refers to the limitation imposed by the solvent on the strength of acids and bases in solution. When a base stronger than the solvent's conjugate base is used, it deprotonates the solvent until the base is entirely consumed, making it ineffective against weaker acids. Conversely, an acid stronger than the solvent's conjugate acid protonates the solvent until the acid is depleted, rendering it ineffective against weaker bases. Essentially, the...
832