c-Cbl-UbcH7複合体の構造:ユビキチン-タンパク質リガゼにおけるRING領域機能
1Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cell
|August 31, 2000
まとめ
RING E3ユビキチンリガゼは,c-Cblのように,脚架として機能する. それらは基質とユビキチン結合酵素 (E2s) に結合し,細胞プロセス調節のためのユビキチン転送を最適化します.
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.
- セルラー・シグナリング
背景:
- ウビキチン-タンパク質結合酵素 (E3s) は,タンパク質のウビキチン化による細胞過程の重要な調節因子である.
- RINGファミリーE3のc-Cblプロトオンコゲンは,活性化受容体チロシンキナーゼをユビキチン化に標的とし,それによってシグナリングを終了します.
- E3-E2-基板相互作用の構造的基礎を理解することは,ユビキチン化メカニズムを解読する鍵です.
研究 の 目的:
- RING E3リガゼc-Cblが同種のユビキチン結合酵素 (E2) と基板ペプチドと相互作用する構造的メカニズムを解明する.
- 異なるE3リガゼファミリー (RINGとHECT) の間のE3-E2相互作用モチーフを比較する.
主な方法:
- X線結晶学を用いて,E2酵素とキナーゼペプチドに結合するc-Cblの構造を決定した.
- RING E3-E2複合体と,以前に決定された HECT E3-E2複合体の比較構造分析が行われました.
主要な成果:
- 結晶構造は,c-Cbl RINGドメインがE2酵素を勧誘する方法を明らかにした.
- RINGとHECTのE3ファミリーに共通するE2モチーフが特定されました.
- 構造は,ペプチド結合領域とE2結合領域の間の硬直な結合を示し,表面チャネルが保存され,基板からE2への転送が容易になりました.
結論:
- RING E3連鎖酵素は,おそらく支架として機能し,効率的なユビキチン転送のために,基板とE2酵素を正確に位置づけます.
- この構造的な洞察は,RING E3が信号伝達経路をどのように制御するかをメカニズム的に理解するためのものです.
- この発見は,主要なE3リガゼファミリー全体でE2募集の保存されたメカニズムを強調しています.
関連する概念動画
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.
01:57Protein 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...
02:58Regulated 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...
00:50Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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.
00:50Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...