ユビキチンリガゼは,プリフォームされたポリユビキチン鎖を結合酵素から基板に転送します
Wei Li1, Daqi Tu, Axel T Brunger
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature
|February 21, 2007
まとめ
研究者は,タンパク質の分解のためのユビキチン鎖の形成を調査した. 彼らは,ユビキチン鎖が基板に結合する前に,酵素 (E2) に前編成されていることを発見し,これはユビキチン-プロテアゾーム系における新しい発見である.
科学分野:
- 細胞生物学 細胞生物学
- 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.
背景:
- ユカリオット細胞は,短命のタンパク質をプロテアソームを通じて分解し,この過程にはユビキチネーションが含まれる.
- ユビキチネーションにはE1,E2,E3酵素が必要で,E3リガゼ (HECTまたはRINGドメイン) がポリユビキチネーションを触媒化する.
- ポリユビキチネーションにおけるE3リガース触媒の正確なメカニズムは,まだ十分に理解されていません.
研究 の 目的:
- E3リガゼ媒介型ポリユビキチネーションのメカニズムを解明する.
- Ube2g2 (E2) とgp78 (E3) がエンドプラズマ網膜に関連した分解経路における役割を調査する.
主な方法:
- マウスUbe2g2とヒトgp78のEscherichia coliにおける再結合表現.
- ポリユビキチン化反応を分析するための生化学分析.
- ユビキチン鎖のプレアセンブリと転送メカニズムの特徴.
主要な成果:
- 実証されたUbe2g2/gp78媒介型ポリユビキチネーションは,Ube2g2の触媒型システインにLys 48結合ユビキチン鎖のプレアセンブリを伴う.
- ユビキチン鎖の延長のための2つのUbe2g2分子間のアミノリシスベースの転送反応を特定しました.
- 組み立てられたユビキチン鎖がUbe2g2から基質のライシン残留物に移行できることを示した.
結論:
- Ube2g2/gp78システムは,プリアセンブリされたユビキチン鎖を含むポリユビキチン化のための新しいメカニズムを使用しています.
- この発見は,E3ユビキチンリガゼの触媒機構に関する新しい洞察を提供します.
- このプロセスを理解することは,エンドプラズマ網膜内の誤折りたたまれたタンパク質の分解に不可欠です.
関連する概念動画
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...
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...
02:58Regulated 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...
01:27Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
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...
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...