信号大麻素受体1-G蛋白复合体的结构
Kaavya Krishna Kumar1, Moran Shalev-Benami2, Michael J Robertson2
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
Cell
|January 15, 2019
概括
研究人员阐明了与MDMB-Fubinaca (FUB) 结合的大麻素受体1 (CB1) 的结构. 这种结构揭示了FUB如何激活CB1-Gi信号, 这对于理解神经疾病治疗至关重要.
科学领域:
- 神经科学
- 生物化学
- 药理学
背景情况:
- 大麻受体1 (CB1) 调解大麻的影响,如情绪改变和缓解疼痛.
- CB1是一种通过Gi蛋白传递信号的G蛋白结合受体 (GPCR).
- 了解CB1-Gi激活是开发神经疾病治疗的关键.
研究的目的:
- 通过合成大麻素MDMB-Fubinaca (FUB) 来激活CB1受体的结构基础.
- 阐明由CB1-FUB复合体激活Gi蛋白的机制.
- 为理解CB1连接体和G蛋白合提供结构框架.
主要方法:
- 使用X射线结晶学来确定CB1-Gi信号复合物的结构.
- 这项研究重点是结合强激素MDMB-Fubinaca (FUB) 的复合物.
主要成果:
- 该结构揭示了FUB如何稳定CB1受体的活性构造.
- 这种稳定促进了Gi蛋白中的核酸交换,从而启动了下游的信号传输.
- 这些发现提供了关于CB1如何激活不同的配体以及它如何与Gi合的见解.
结论:
- 确定结构提供了合成大麻素对CB1受体激活的分子理解.
- 这种知识对于设计针对CB1-Gi途径的治疗药物至关重要.
- 这项研究揭示了受体的G蛋白合和选择性机制.
相关概念视频
G-protein Coupled Receptors
132.0K
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.
132.0K
Protein and Protein Structure
87.5K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
87.5K
Protein Complex Assembly
16.7K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.7K
Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
Assembly of Signaling Complexes
6.6K
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,...
6.6K
Structural Protein Function
29.9K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
29.9K


