相关实验视频

Updated: Sep 13, 2025

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Published on: January 9, 2015

氨基酸传感器的冷EM结构与人类GATOR2复合体结合

Ming-Yuan Su¹, Fei Teng², Shan Wang³

¹Department of Biochemistry, Key University Laboratory of Metabolism and Health of Guangdong, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China.

|July 31, 2025

概括

这项研究揭示了营养传感器CASTOR1和Sestrin2如何抑制GATOR2复合体,这对mTORC1通路调节至关重要. 结构和动态分析澄清了GATOR2的情况.

科学领域:

细胞生物学细胞生物学
分子机制的分子机制
信号传输信号传输

背景情况:

哺乳动物细胞通过mTORC1通路控制生长,整合环境信号.
在mTORC1调节过程中,GATOR2复合体 (WDR59,WDR24,Mios,Sec13,Seh1l) 是mTORC1调节的核心.
氨基酸的可用性通过像Sestrin2和CASTOR1这样的传感器决定了mTORC1的活动,这些传感器抑制了GATOR2.2.

研究的目的:

阐明氨基酸传感器抑制GATOR2复合物的结构机制.
了解GATOR2及其抑制传感器之间的动态相互作用.
提供有关营养感应和mTORC1通路调节的见解.

主要方法:

低温电子显微镜 (cryo-EM) 用于在抑制状态下确定GATOR2的结构.
-交换质谱法 (HDX-MS) 用于分析蛋白质动态.
生物化学试验用于研究GATOR2,Sestrin2和CASTOR1.1之间的相互作用.

主要成果:

化EM结构揭示了CASTOR1如何结合Mios和Sestrin2如何结合WDR24-Seh1l亚复合体.
传感器结合会导致GATOR2.2.中的形状变化.
HDX-MS数据显示GATOR2和传感器复合体中的动态运动,由氨基酸水平调节.

结论:

这项研究阐明了氨基酸传感器抑制GATOR2的分子基础.
结构和动态洞察力揭示了如何感知营养的可用性来调节mTORC1.1.
这项工作加深了我们对控制细胞生长的营养感应机制的理解.

关键词:

卡斯托尔 (Castor) 是一个名字.CP:新陈代谢过程中的新陈代谢.科普:分子生物学分子生物学在 GATOR1 的位置上.在GATOR2中,我们可以使用GATOR2.在HDX-MS中使用HDX-MS.这就是Sestrin2的原因.氨基酸感应是一种氨基酸感应.低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.mTOR复合体 1 1 的情况.

更多相关视频

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Published on: March 16, 2020

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

相关概念视频

Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Protein Folding

Protein Folding

Transducer Mechanism: G Protein–Coupled Receptors

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...

GPCR Desensitization

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

G Protein-coupled Receptors

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...