短寿命蛋白质中的降解信号
1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Cell
|March 24, 1989
概括
这项研究确定了蛋白质降解信号中的第二个关键决定因素:一种特定的氨酸残留物. 这一发现与N端残留一起,完成了我们对蛋白质稳定性和循环的理解.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 酵母遗传学 酵母遗传学
背景情况:
- 之前的研究已经确定了N端残留物作为蛋白质降解信号的组成部分.
- 了解完整的蛋白质降解信号对于控制蛋白质稳定性和周转至关重要.
研究的目的:
- 通过识别额外的决定因素来定义完整的氨基终端降解信号.
- 阐明新发现的决定因素在蛋白质降解中的机械作用.
主要方法:
- 在酵母 (Saccharomyces cerevisiae) 中表达了具有不同N端残留和延伸的修饰二叶酸还原酶蛋白.
- 这些工程蛋白质的体内半衰期的比较.
- 在目标的短寿命蛋白质中分析乌比奎-乌比奎结合链.
主要成果:
- 氨基终端降解信号包括两个不同的决定因素:N终端残留物和特定的氨酸残留物.
- 氨酸残留的功能独立于周围的氨基酸序列.
- 短寿命蛋白质中的乌比基-乌比基结合物局部存在于这种已识别的氨酸残留物中.
结论:
- 完整的N端降解信号包括N端残留物和特定的内部氨酸残留物.
- 这种氨酸残留物作为乌比奎结合的关键部位,调解蛋白质降解.
- 这些发现为酵母中蛋白质循环调节提供了更全面的模型.
相关概念视频
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02:51mRNA Stability and Gene Expression
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Cis-acting Elements involved in mRNA stability
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02:27Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
02:58Regulated Protein Degradation
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...
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01:13The Proteasome
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