对PTPN21的结构分析显示,FERM域对其酸酶活性具有主导负效应
Lu Chen1,2, Zijun Qian3, Yuyuan Zheng2,4
1Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
Science advances
|February 28, 2024
概括
蛋白氨酸酸酶N21 (PTPN21) 活性较弱,并通过其FERM域进行自身抑制. 破坏这种相互作用可以增强ERK信号,提供对PTPN21的洞察力.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 蛋白氨酸酸酶N21 (PTPN21) 是FERM域含有PTP家族的一员,对于细胞骨相关的细胞过程至关重要.
- PTPN21的酸酶域含有WPE循环,与正规的WPD循环不同,导致假设缺乏催化活性,尽管其已知的功能.
- 将PTPN21的结构特征与其生物作用相协调,需要了解其催化活性和调节.
研究的目的:
- 阐明PTPN21调节的结构和生化基础.
- 调查PTPN21.21的FERM和PTP域之间的相互作用.
- 了解PTPN21通过HPV18 E7.7等致癌蛋白调节的机制.
主要方法:
- 确定单个PTPN21FERM和PTP域的晶体结构,以及FERM-PTP复合体.
- 生物化学分析以评估PTPN21的催化活性和调节机制.
- 研究HPV18 E7型蛋白和PTPN21之间的相互作用.
主要成果:
- PTPN21表现出较弱的催化活性,并且通过其FERM域与PTP域的关联来自我抑制.
- 破坏FERM-PTP相互作用导致细胞外信号调节激酶 (ERK) 激活的增强.
- 致癌性HPV18 E7蛋白在FERM域结合部位与PTPN21结合,这表明FERM域位移的机制.
结论:
- PTPN21是一种由其FERM域调节的催化弱,自身抑制的酶.
- FERM-PTP相互作用对PTPN21的基底活性和调节至关重要.
- HPV18 E7可能通过移位FERM域来调节PTPN21活动,从而影响细胞信号通路.
相关概念视频
02:54Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
01:42Phosphoinositides and PIPs
8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
01:02Phosphorylation
50.3K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.3K