与G蛋白结合的受体在模型双层的动态模拟中自我组装
Xavier Periole1, Thomas Huber, Siewert-Jan Marrink
1Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. x.periole@rug.nl
Journal of the American Chemical Society
|July 31, 2007
概括
膜蛋白自组合,特别是G蛋白合受体 (GPCRs),受到脂双层特性的影响. 跨膜螺旋体附近的局部膜变形决定了蛋白质的关联率和方向.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 膜蛋白的动力学 膜蛋白的动力学
背景情况:
- 综合膜蛋白,包括G蛋白结合受体 (GPCRs),形成寡合结构.
- 在膜中GPCR自我组装的机制和生理意义仍然在很大程度上是未知的.
研究的目的:
- 研究视觉罗多素自我组装的分子基础.
- 使用计算模型确定脂双层特性如何影响GPCR自我组装.
主要方法:
- 使用粗粒分子动力学 (CGMD) 模型进行大规模模拟.
- 模拟系统最多有16个罗多普辛分子,蛋白质与脂质的比例为1:100,持续时间长达8微秒.
- 分析了四种不同的脂环境.
主要成果:
- 在2号,4号和7号跨膜螺旋附近确定了可复制的局部化膜双层适应.
- 证明局部膜变形对于蛋白质与蛋白质的关联至关重要.
- 显示了膜性质决定了罗多素组装的速度,范围和方向.
结论:
- 局部膜变形是膜蛋白自组合的关键因素.
- 这些发现提供了对膜蛋白质寡合化的概括机制的见解.
- 表明膜物理化学特性和蛋白质组装动态之间存在联系.
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.
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,...
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...
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...


