人类GATOR1和GATOR1-Rag GTPase复合物的结构
Kuang Shen1,2,3,4, Rick K Huang5, Edward J Brignole2,6
1Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 455 Main Street, Cambridge, Massachusetts 02142, USA.
Nature
|March 29, 2018
概括
研究人员阐明了GATOR1复合体的结构,通过调节Rag GTPases揭示了它在营养感应中的作用. 这一发现揭示了一种控制mTORC1通路的新机制.
科学领域:
- 细胞生物学
- 分子机制
- 信号传输
背景情况:
- 通过mTORC1途径调节细胞生长.
- 由DEPDC5,NPRL2和NPRL3组成的GATOR1复合体作为Rag GTPases的GTPase激活蛋白 (GAP),控制mTORC1.
- 由于其独特的蛋白质成分,GATOR1的分子功能和结构仍然未知.
研究的目的:
- 确定GATOR1复合物的分子结构及其与Rag GTPases的相互作用.
- 阐明GATOR1调节Rag GTPases和mTORC1信号的机制.
- 了解mTORC1通路中的营养感应的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 解决了GATOR1和GATOR1-Rag GTPase复合物的结构.
- 进行生物化学分析以描述相互作用和酶活性.
主要成果:
- GATOR1综合体呈现出一个扩展的建筑结构,其中有一个中央腔.
- DEPDC5直接与RAGA相互作用,抑制GTP水解,而NPRL2- NPRL3异构体则通过较弱的相互作用调节GAP活性.
- 该结构显示GATOR1和Rag GTPases之间至少有两个不同的结合模式.
结论:
- 这项研究揭示了GATOR1复合体的分子结构,这是mTORC1营养感应途径的关键组成部分.
- 在GAP (GATOR1) 和其基质GTPase (Rag) 之间阐明了一种非正规的相互作用机制.
- 这些发现提供了关于细胞如何感知营养和调节生长的见解.
相关概念视频
02:14GTPases and their Regulation
9.9K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.9K
02:14GTPases and their Regulation
3.0K
3.0K
01:33Coat Assembly and GTPases
4.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
4.5K
01:24Small GTPases - Ras and Rho
5.5K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.5K
01:14Polymer Classification: Architecture
3.9K
Polymers are classified as linear or branched on the basis of their chain architecture. The polymer chains in linear polymers have a long chain-like structure with minimal to no branching at all. Even if a polymer features large substituent groups on the monomer, which appear as branches to the skeleton, it is not considered a branched polymer. A branched polymer contains secondary polymer chains that arise from the main polymer chain. The branching occurs when the polymer growth shifts from...
3.9K
02:41Protein Complex Assembly
16.9K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.9K