通过细胞质和线粒体的甲素进行调节的蛋白质脱化
Moran Benhar1, Michael T Forrester, Douglas T Hess
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
概括
铁素酶调节蛋白质的脱化,这是一个关键的细胞信号传递过程. 这项研究确定了 thioredoxin-1 和 thioredoxin-2 作为caspase-3 的关键denitrosylases,影响细胞信号传递和细胞亡.
科学领域:
- 生物化学 生物化学
- 细胞信号传输 细胞信号传输
- 分子生物学分子生物学
背景情况:
- 氧化 (NO) 在细胞信号传导中通过氨酸残留物的S-化非常重要.
- 控制蛋白质脱化,去除NO修饰的机制在细胞信号传输中基本上是未知的.
- 了解denitrosylase活性对于阐明NO介导的细胞过程至关重要.
研究的目的:
- 为了确定负责蛋白质脱酶化的酶活性.
- 为了研究特定的denitrosylases在调节caspase-3中的作用.
- 探索基底和刺激诱导的蛋白质脱的机制.
主要方法:
- 生物化学查以确定化酶活性.
- 专注于caspase-3作为一个模型基质为denitrosylation.
- 利用人类淋巴细胞和Fas刺激来研究细胞反应.
- 抑制硫素-硫素还原酶以识别基质.
主要成果:
- 鉴定出硫素和硫素还原酶是丁酸酶活动.
- 在休息的淋巴细胞中, thioredoxin-1 脱化细胞酶-3 保持低S-化.
- 在Fas刺激后,铁素-2调解了线粒体相关的caspase-3的脱化,促进了激活和亡.
- 抑制研究揭示了内源性S-化酶的额外基质.
结论:
- 特定的氨酸酶 (氨酸-1和氨酸-2) 作为氨酸酶起作用.
- 这些酶在调节基底和刺激诱导的caspase-3的S-nitrosylation中发挥着不同的作用.
- 硫素系统对于控制哺乳动物细胞中的蛋白质脱至关重要,影响细胞信号传递和细胞亡.
相关概念视频
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Translocation of Proteins into the Mitochondria
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,...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

