在双层中,G蛋白结合受体的高分子组织的结构决定因素
Xavier Periole1, Adam M Knepp, Thomas P Sakmar
1Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands. x.periole@rug.nl
Journal of the American Chemical Society
|June 12, 2012
概括
G蛋白结合受体 (GPCR) 罗多素在细胞膜中形成稳定的二次体. 分子动力学模拟揭示了由特定螺旋相互作用驱动的首选尾对尾形状,这对于理解GPCRs至关重要.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 像罗多素这样的G蛋白结合受体 (GPCR) 在本地膜中自组装.
- 对于GPCR寡合化的结构基础在很大程度上是未知的.
- 了解这些相互作用是GPCR功能的关键.
研究的目的:
- 阐明罗多素自我组装成超分子结构的结构决定因素.
- 为了确定罗多普辛的偏好相互作用模式和稳定的二分体构造.
- 为研究跨膜蛋白质二元化建立一个通用的计算策略.
主要方法:
- 在模型膜中模拟罗多素的粗粒度分子动力学 (CGMD).
- 模拟扩展到100μs,涉及多达64个罗多素分子.
- 雨采样和潜在的平均力 (PMF) 计算来分析受体-受体相互作用.
主要成果:
- 确定了罗多素分子之间的强烈偏好相互作用模式.
- 揭示了两个主要的受体-受体相互作用模式,没有能量屏障,可以形成稳定的二元体.
- 首选的罗多普辛二聚体采用了一种涉及跨膜螺旋体H1/H2和两螺旋体H8.8的尾到尾形状.
结论:
- 罗多普辛在尾到尾的方向上形成稳定的二次体,与实验数据相一致.
- 不太稳定,脂质覆盖的二极体通过涉及H4和H6螺旋体的相互作用而稳定.
- CGMD方法适用于研究GPCR和其他跨膜蛋白的二元化.
相关概念视频
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
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...
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 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.


