相关实验视频
Updated: Jun 16, 2026

13:21
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
通过Smac/DIABLO激活apoptotic的结构和生化基础
Nature
|September 6, 2000
概括
Smac/DIABLO蛋白通过与抑制蛋白 (IAP) 结合并释放caspases来激活亡. 它的结构揭示了功能必不可少的同位体接口,在物种之间得到保护.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 细胞亡,或编程细胞死亡,对于元生动物的发育和恒常性至关重要,由管调节.
- 亡蛋白抑制剂 (IAP) 抑制体,控制细胞死亡.
- 一种线粒体蛋白质Smac/DIABLO对抗IAP,促进细胞亡.
研究的目的:
- 为了阐明Smac/DIABLO激活亡的机制.
- 为了确定Smac/DIABLO的功能结构基础.
- 调查Smac/DIABLO在其活动中的同质化和N端的作用.
主要方法:
- 在2.2A分辨率下测定Smac/DIABLO结构的X射线晶体学.
- 位点定向突变发生,以评估二维接口的功能.
- 在体外测试中使用来自Smac/DIABLO的N端的来研究procaspase-3激活.
主要成果:
- Smac/DIABLO通过一个广泛的疏水界面进行同质化,这对其功能至关重要.
- 破坏二次接口的突变显著损害了Smac/DIABLO的亲亡活动.
- 来自Smac/DIABLO的N端的有效地激活了Procaspase-3在体外,类似于Drosophila蛋白质.
结论:
- Smac/DIABLO与IAP的物理相互作用是激活procaspase-3和成熟caspase-3的关键.
- 通过特定的疏水界面进行同质化对于Smac/DIABLO的功能至关重要.
- Smac/DIABLO的N端在亡激活中起着至关重要的作用,证明了进化保护.
相关概念视频
Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...

