寡聚化RIPK1是CD95体的主要核心组成部分
Nikita V Ivanisenko1, Corinna König1, Laura K Hillert-Richter1
1Translational Inflammation Research, Medical Faculty, Otto von Guericke University, Magdeburg, Germany.
The EMBO journal
|April 16, 2025
概括
研究人员确定了体的核心结构,这是一个细胞死亡信号平台,对炎症至关重要. 这一发现有助于更好地理解亡和潜在的治疗点炎症性疾病.
科学领域:
- 分子生物学分子生物学
- 细胞死亡信号传递
- 结构生物学 结构生物学
背景情况:
- 体是一个关键的信号平台,它启动了亡,这是一个参与炎症的编程细胞死亡途径.
- 了解体的组成和结构对于破译其在多细胞生物中的作用至关重要.
- 以前对体细胞分子结构的了解并不完整.
研究的目的:
- 为了阐明CD95L/BV6诱导性体的组成,并得出一个结构模型.
- 识别体内的中心成分及其结构组织.
- 研究特定分子相互作用在死体组合和死体灭诱导中的作用.
主要方法:
- 利用生物化学测试来分析蛋白质相互作用.
- 采用定量质谱法来确定体组合.
- 应用AlphaFold建模以获得结构洞察力,并得出了体的结构模型.
主要成果:
- 确定了RIPK1作为形成死体细胞核的中心组成部分.
- 阿尔法折模拟揭示了RIPK1寡合化的结构机制.
- 突出了FADD和RIPK1死亡域 (DD) 之间的II型相互作用在复杂组合中的关键作用,通过突变发生验证.
结论:
- 该研究提供了详细的体结构模型,以RIPK1.1为中心.
- 类型IIDD相互作用对RIPK1-介导的复合组合和亡至关重要.
- 这些发现为在炎症性疾病中药理学向死细胞灭绝途径提供了潜在的潜力.
更多相关视频
09:15Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
Published on: October 20, 2022
2.1K
07:17Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
2.5K
相关概念视频
Necrosis
3.6K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
3.6K
The Extrinsic Apoptotic Pathway
5.5K
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...
5.5K
The Intrinsic Apoptotic Pathway
5.6K
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...
5.6K
Phagocytosis of Apoptotic Cells
3.1K
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...
Normal cells contain receptors that prevent them from being recognized...
3.1K
Overview of Cell Death
5.6K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
5.6K
Export of Misfolded Proteins out of the ER
3.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.3K
