一个c-Cbl-UbcH7复合物的结构:Ubiquitin-protein ligases中的RING域功能
1Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cell
|August 31, 2000
概括
和c-Cbl一样,RING E3泛素化酶的功能是脚手架. 它们结合基质和泛素结合酶 (E2s),优化泛素转移以调节细胞过程.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 乌比基-蛋白质酶 (E3s) 是通过蛋白质乌比基化细胞过程的关键调节者.
- 一个RING家族E3的c-Cbl原瘤基因,准了受体激活氨酸激酶的无处不在,从而终止了信号传输.
- 了解E3-E2-基底相互作用的结构基础是解读无处不在机制的关键.
研究的目的:
- 阐明RING E3结合酶c-Cbl与其同源的泛基素结合酶 (E2) 和基质相互作用的结构机制.
- 为了比较不同E3酶家族 (RING和HECT) 的E3-E2相互作用动机.
主要方法:
- 采用X射线晶体学,确定c-Cbl与E2酶和激酶结合的结构.
- 在RING E3-E2复合体和先前确定的HECT E3-E2复合体之间进行了比较结构分析.
主要成果:
- 晶体结构揭示了c-Cbl RING域是如何招募E2酶的.
- 确定了一个由RING和HECT E3家族都认可的共同E2图案.
- 该结构显示了结和E2结合域之间的刚性合,并保留了表面通道,以促进基质到E2的转移.
结论:
- 环E3链酶可能充当支架,精确地定位基质和E2酶,以有效地转移无处不在素.
- 这种结构洞察力为RING E3s如何调节信号通路提供了机械的理解.
- 这些发现突出了主要E3酶家族中E2招募的保存机制.
相关概念视频
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...