在cFLIP-procaspase-8和cFLIP-procaspase-8-FADD复合体中的反向等级DED组件
Chao-Yu Yang1, Yi-Chun Tseng1,2, Yi-Fan Tu2
1Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan.
Nature communications
|October 17, 2024
概括
细胞FLIP (cFLIP) 与 FADD 独立的 procaspase-8 形成了新的复合体,揭示了瘤细胞中细胞死亡抵抗和不死亡的新机制.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 结构生物学 结构生物学
- 癌症生物学 癌症生物学
背景情况:
- 细胞FLIP (cFLIP) 是细胞亡的关键调节剂,在癌细胞中经常过度表达.
- 在此之前,cFLIP在调节死亡信号复合物的精确结构机制是未知的.
研究的目的:
- 阐明cFLIP介导的死亡效应域 (DED) 综合体的三维结构.
- 揭示控制细胞死亡途径的调节机制,涉及cFLIP和 procaspase-8.
主要方法:
- 结晶结构的确定 结晶结构的确定
- 低温电子显微镜 (cryo-EM) 是一种电子显微镜.
- 结构引导的突变发生实验 结构引导的突变发生实验
主要成果:
- 揭示了由cFLIP和 procaspase-8组成的非传统的双联DED复合体,独立于FADD.
- 证明这个复合体会招募FADD,在所有学上调节cFLIP,并部分激活RIPK1裂变的caspase-8.
- 提供了对亡和亡抵抗机制的见解.
结论:
- cFLIP 和 procaspase-8 形成一个FADD 独立的复合体,影响细胞死亡信号.
- 这一发现为多蛋白螺旋组合如何控制细胞命运决定和不朽性提供了一个统一的模型.
相关概念视频
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Membrane Asymmetry Regulating Transporters
4.3K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.3K
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
Export of Misfolded Proteins out of the ER
3.5K
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...
3.5K
Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
The Extrinsic Apoptotic Pathway
6.3K
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...
6.3K


