环菲林D的N端裂解增强了其结合F-ATP合成酶的能力
Gabriele Coluccino1, Alessandro Negro2, Antonio Filippi1
1Department of Medicine, University of Udine, 33100, Udine, Italy.
Communications biology
|November 11, 2024
概括
一种新型的循环素D (CyPD) 的截断形式缺乏其N端,可以更有效地与线粒体F-ATP合成酶结合. 这种由calpain 1介导的裂变机制表明了调节酶活性的新方法,具有潜在的病理生理学意义.
科学领域:
- 线粒体生物学 线粒体生物学
- 酶调节酶的调节
- 蛋白质的生物化学 蛋白质的生物化学
背景情况:
- 环素D (CyPD) 调节了线粒体的F-ATP合成酶.
- CyPD的N端含有特定物种的特征.
研究的目的:
- 为了研究一个新发现的CyPD (ΔN-CyPD) 的截断形式,缺乏N-终端残留物.
- 与全长CyPD (FL-CyPD) 相比,阐明ΔN-CyPD与F-ATP合成酶的相互作用.
- 为了确定负责生成ΔN-CyPD的细胞蛋白酶.
主要方法:
- 核磁共振 (NMR) 谱学用于研究蛋白质结构和灵活性.
- 生物化学测试以评估CyPD与F-ATP合成酶的结合.
- 细胞研究以确定参与ΔN-CyPD生成的蛋白酶.
主要成果:
- FL-CyPD的N端是高度灵活的,而核心是刚性的.
- 与FL-CyPD不同的是,ΔN-CyPD与盐水中F-ATP合成酶的OSCP子单元结合.
- CyPD的N端显著降低了其与OSCP的结合亲和力.
- 卡尔帕因1被确定为负责在细胞中产生ΔN-CyPD的蛋白酶.
结论:
- 通过N-终端切割存在调节CyPD活动的新机制.
- ΔN-CyPD表现出对F-ATP合成酶的结合特性发生变化.
- 这种由calpain 1介导的裂变事件对线粒体功能有潜在的病理生理学影响.
相关概念视频
ATP Synthase: Structure
11.9K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
11.9K
Allosteric Proteins-ATCase
5.7K
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...
5.7K
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
3.0K
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,...
3.0K
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K


