β-arrestin1 是一个E3的ubiquitin结合酶适配器,用于基质线性聚基化
Chandler J McElrath1, Sara Benzow1, Ya Zhuo1
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
The Journal of biological chemistry
|November 19, 2023
概括
β-arrestin 1 (βarr1) 作为一个桥梁,将信号传导适配分子1 (STAM1) 与E3结合酶连接起来. 这种相互作用促进STAM1的线性无所不在,影响G蛋白结合受体 (GPCR) 信号传输.
科学领域:
- 蜂信号传输是如何进行的
- 分子生物学分子生物学
- 蛋白质的无处不在化
背景情况:
- G蛋白结合受体 (GPCR) 信号传递和贩运受到翻译后修饰的调节,特别是由E3泛素连接酶的泛素化.
- 虽然已知E3链酶可在GPCR和效应分子中无处不在,但涉及βarrestins的确切机制尚不清楚.
研究的目的:
- 阐明βarrestin1 (βarr1) 在通过E3结合酶对效应蛋白进行无处不在的机制性作用.
- 为了研究βarr1,信号转换适配分子1 (STAM1) 和氨酸相互作用蛋白4 (AIP4) 之间的相互作用.
主要方法:
- 开发一种体外复制系统,以研究蛋白质相互作用.
- 质谱测量用于识别STAM1.1上的ubiquitination位点和ubiquitin联系.
- 细胞测试用于评估特定氨酸残留物在蛋白质相互作用和GPCR激活中的作用.
主要成果:
- βarrestin1 (βarr1) 作为STAM1和E3结合酶缩蛋白相互作用蛋白4 (AIP4) 之间的适配器.
- 在STAM1上确定了7个氨酸残留物作为泛化部位,βarr1在氨酸136上促进了线性聚氨酸链的形成.
- 在STAM1上素136对于稳定GPCR激活后的βarr1:STAM1相互作用至关重要.
结论:
- 氨酸相互作用蛋白4 (AIP4) 被确定为能够形成线性无素链的少数E3链酶之一.
- 这些发现表明线性无素链在调节G蛋白合受体 (GPCR) 信号和贩运通路方面发挥了新的作用.
相关概念视频
Regulated Protein Degradation
7.3K
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...
7.3K
GPCR Desensitization
6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
Assembly of Signaling Complexes
5.8K
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,...
5.8K
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
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K


