ユビキチン系における酵素の調節のための戦略
Andreas Ernst1, George Avvakumov, Jiefei Tong
1Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.
Science (New York, N.Y.)
|January 5, 2013
まとめ
研究者は,ユビキチンシステムを正確に制御するために,新しいユビキチン変種を開発しました. これらの変種はデウビキキチナゼを阻害したり,酵素活性を増強したりすることができ,細胞機能を調節する新しい方法を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- ユビキチン系は,多様な細胞過程の調節に不可欠です.
- ユビキチン化に関与する酵素をターゲットにすることは,細胞機能を理解し,操作するために不可欠です.
研究 の 目的:
- ユビキチン系内の酵素を標的とする方法を開発する.
- 特定の酵素活性を調節できるユビキチン変種を作成する.
主な方法:
- Ubiquitinの多様性の豊富な組み合わせライブラリを利用した.
- 4つのデウビキキチナゼ (DUB) の阻害剤を開発し,結晶学で複合体を分析した.
- ユビキチン結合 (E2) とリガゼ (E3) 酵素への選択を拡大した.
主要な成果:
- DUBsを阻害するユビキチン変種を特定しました.
- ユビキチン変種がE2およびE3酵素活性を増強することが示された.
- ユビキチン変種がユビキチン結合ドメインに選択的に結合することを示した.
- 細胞文脈におけるユビキチン変種の選択的機能を観察した.
結論:
- ユビキチン変種は,ユビキチンシステムの正交調節のための多用途なツールを提供します.
- このアプローチは,ユビキチネーション経路における特定の酵素的ステップの正確な制御を可能にします.
- この発見は,ユビキチン媒介プロセスを標的とした治療的介入のための新しい道を開く.
関連する概念動画
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...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:17The Proteasome Structure
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...