针对细胞内降解的自受体灵感抗体融合蛋白
Journal of the American Chemical Society
|September 25, 2023
概括
研究人员开发了新型自受体启发的向嵌合体 (AceTACs) 来降解不需要的蛋白质聚合物和器官. 这一突破提供了一种针对细胞内降解的新方法,
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 自会降解像蛋白质聚合物和有机体这样的大细胞内成分.
- 由于病态积累,自功能受损与衰老和神经退行性疾病有关.
- 目前用于哺乳动物细胞中聚合物或有机体的向降解方法有限.
研究的目的:
- 开发一种广泛适用的蛋白质聚合物和细胞器的向降解方法.
- 创建新的自受体启发的向模拟体 (AceTAC).
- 研究AceTACs在降解特定细胞点中的有效性.
主要方法:
- 设计的基于抗体融合的AceTAC降解剂模仿自受体.
- AceTACs被设计为同时与细胞标和LC3蛋白在自细胞膜上结合.
- 对容易聚合的蛋白质 (huntingtin,TDP-43,FUS突变体) 和有机体 (线粒体,过氧体,ER) 的降解进行了测试.
主要成果:
- 成功开发出诱导聚合易受蛋白质和蛋白质聚合物的向降解的AceTAC.
- 证明了AceTACs降解各种器官的能力,包括线粒体,过氧体和内质网膜.
- AceTACs有效地将细胞标运送到自-解体通路进行降解.
结论:
- 开发的AceTAC系统提供了利用自的新型抗体降解策略.
- 这项技术显著扩大了细胞内向降解技术的范围.
- AceTACs为未来的基于抗体的自降解方法提供了设计原则.
更多相关视频
05:33High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
9.7K
11:05Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
Published on: February 21, 2019
9.1K
相关概念视频
Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Autophagy
4.3K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.3K
Regulated Protein Degradation
7.4K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.4K
Delivery Pathways to the Lysosome
6.6K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
Phagocytosis of Apoptotic Cells
3.9K
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...
3.9K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
