在apoptosome中CARD域的相互作用的计算表征
Rita Ortega-Vallbona1, Linda Johansson2, Laureano E Carpio1,3
1ProtoQSAR SL, Parque Tecnológico de Valencia, Paterna, Valencia 46980, Spain.
Biochemistry
|January 6, 2025
概括
这项研究以计算方式分析了酶激活和招募域 (CARD) 在细胞体中的相互作用,确定了Apaf-1和酶-9结合的关键残留物,并证实了相互作用的特异性.
科学领域:
- 分子生物学分子生物学
- 计算生物学 计算生物学
- 生物化学 生物化学
背景情况:
- 细胞突变体通过蛋白质复杂相互作用调节细胞突变,特别是涉及含有蛋白质的卡斯帕酶激活和招募域 (CARD).
- 了解这些CARD-CARD相互作用的特异性和稳定性对于阐明亡途径至关重要.
研究的目的:
- 通过计算分析apoptosome中的CARD-CARD相互作用的稳定性和特异性.
- 为了确定参与Apaf-1和Caspase-9 CARD域之间的相互作用的关键残留物.
- 通过比较原生和交叉对接的复合体来研究 CARD-CARD 相互作用的特异性.
主要方法:
- 蛋白质与蛋白质对接的共识方法.
- 对 CARD-CARD 相互作用的计算分析.
- 在apoptosome和PIDDosome组件之间进行交叉对接实验.
主要成果:
- 确定了Apaf-1和Caspase-9 CARD域相互作用的重要残留物.
- 使用可用的实验复杂结构验证了计算方法.
- 证明本地相互作用比交叉对接相互作用更稳定,证实了特异性.
结论:
- 已识别的关键残留物在细胞细胞体活动中发挥着关键作用,并为干预提供了目标.
- 计算方法在研究复杂的蛋白质-蛋白质相互作用方面是有效的.
- 这项工作加深了对亡调节机制的理解.
相关概念视频
The Extrinsic Apoptotic Pathway
6.2K
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...
6.2K
The Intrinsic Apoptotic Pathway
6.4K
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...
6.4K
Caspases
12.3K
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...
12.3K
Apoptosis
11.1K
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...
11.1K
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Phagocytosis of Apoptotic Cells
3.7K
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...
3.7K


