相关实验视频
Updated: Aug 13, 2026

10:13
Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
细胞外gp130细胞因子受体信号复合体的结构
1Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305, USA.
概括
卡波西的肉瘤相关的疹病毒编码了一个病毒性互白素-6 (IL-6) 激活人类gp130.0. 病毒IL-6使用疏水相互作用来增强结合,与人类IL-6不同.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 病毒学 病毒学
背景情况:
- gp130是细胞因子的信号转导受体,通过连接体结合和复杂的寡合化来激活.
- 卡波西的肉瘤相关性疹病毒 (KSHV) 产生一种病毒IL-6同源,激活人类gp130.0.
研究的目的:
- 阐明病毒IL-6结合和激活人类gp130.0.的结构基础.
- 了解KSHV对宿主细胞因子信号传递的操纵背后的分子机制.
主要方法:
- 使用X射线晶体学来确定病毒IL-6/gp130复合物的2.4安格斯特罗姆结构.
- 分析信号组件内的蛋白质-蛋白质相互作用和结合接口.
主要成果:
- 晶体结构显示了由两个病毒IL-6/gp130单元组成的四重复合体.
- 在gp130免疫球蛋白域和病毒IL-6位点III之间直接相互作用对于受体激活至关重要.
- 病毒IL-6利用疏水性氨基酸进行gp130结合,与人类IL-6的疏水性相互作用相比,增强了接口互补性.
- gp130的两路结合部位表现出可塑性,有助于与病毒IL-6的交叉反应.
结论:
- 该研究揭示了病毒IL-6通过特定的疏水相互作用激活人类gp130的结构机制.
- 这些发现突出了病毒适应策略,以劫持宿主信号通路.
- 了解这些相互作用可以为针对病毒性细胞因子同类的治疗策略提供信息.
相关概念视频
G-protein Coupled Receptors
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.
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
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...
Activation and Inactivation of G Proteins
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 affinity and are together...
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...
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...
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, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...

