Gα C-终端删除对内在GDP释放/GTPase活动和 conformational动态的影响
Junyoung Kim1, Ka Young Chung1
1School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Journal of structural biology
|March 1, 2025
概括
G蛋白的C端波形对Gαs的功能至关重要,影响其生物化学性质和结构动态. 这种结构元素具有亚型特异性影响,影响G蛋白信号传递.
科学领域:
- 分子生物学分子生物学
- 生物化学 生化学
- 细胞信号传递 细胞信号传递
背景情况:
- 异构G蛋白 (G蛋白) 从G蛋白结合受体 (GPCR) 中传递信号.
- G蛋白活性是由Gα子单元的关二酸盐 (GDP) 或关三酸盐 (GTP) 结合状态调节的.
- 已知称为"波形"的Gα C-终端5残留物对GPCR结合和合选择性至关重要.
研究的目的:
- 为了研究波形截断对G蛋白的内在生化特性所起的作用.
- 确定波形对GDP/GTP周转率,GTPase活动以及Gαs和Gαi1.i的构造动态的影响.
主要方法:
- 使用BODIPY标记的核酸来研究核酸周转.
- 采用/交换质谱法 (HDX-MS) 来分析形状动态.
- 研究了Gαs和Gαi1亚型中GαC终端波形的截断.
主要成果:
- 波形截断显著改变了GDP/GTP的周转率,GTPase活动和Gαs的结构灵活性.
- 通过Gαs的α1区域的p-循环在波形截断时显示出显著的灵活性变化.
- 波形的切断对Gαi1.1的内在性质的影响很小.
结论:
- G蛋白波动对G蛋白稳定性和形状动态表现出亚型特异性影响.
- 像波形子这样的结构元素在调节G蛋白功能的过程中起着至关重要的作用.
- 这些发现对理解GPCR信号传递机制和药物开发有意义.
更多相关视频
13:51Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
Published on: November 11, 2018
9.8K
09:40Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
17.9K
相关概念视频
Activation and Inactivation of G Proteins
6.5K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.5K
GTPases and their Regulation
8.2K
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,...
8.2K
Small GTPases - Ras and Rho
3.9K
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:
3.9K
G-protein Coupled Receptors
114.3K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
114.3K
Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
G Protein-coupled Receptors
11.0K
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...
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...
11.0K
