人类CB1大麻素受体的高分辨率晶体结构
Zhenhua Shao1, Jie Yin1, Karen Chapman1
1Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|November 17, 2016
概括
研究人员确定了与抑制剂结合的人类CB1受体的首个高分辨率结构. 这种对大麻素受体结构的原子层次洞察力有助于发现治疗疼痛和等疾病的药物.
科学领域:
- 生物化学
- 结构生物学
- 药理学
背景情况:
- 人类大麻素受体 (CB1和CB2) 是G蛋白合受体 (GPCRs) 介导对THC等内分泌大麻素和植物大麻素的反应.
- 这些受体是药物发现的关键目标,因为它们在疼痛,和肥胖中具有治疗潜力.
- 缺乏大麻素受体的高分辨率结构数据,阻碍了机理学的理解.
研究的目的:
- 确定人类CB1受体的高分辨率结构.
- 为了解大麻素受体功能和配体相互作用提供原子框架.
- 促进对内分泌系统的新型治疗调节剂的设计.
主要方法:
- 使用了GPCR工程技术.
- 使用脂质立方相结晶来获得合适的晶体.
- 使用X射线结晶学以2.6Å分辨率确定结构.
主要成果:
- 人类CB1受体与抑制剂taranabant结合的结构以2. 6分辨率确定.
- 包括N端区域在内的CB1的细胞外表面形成了一个独特的联结口袋.
- 接研究表明这种口袋可以容纳激素THC,提供对激素结合的见解.
结论:
- 确定CB1受体结构为理解大麻素信号提供了原子基础.
- 这种结构信息对于合理设计和优化向内分泌系统的药物至关重要.
- 这些发现为开发各种由大麻素受体调节的疾病新疗法铺平了道路.
更多相关视频
18:45Harvesting and Cryo-cooling Crystals of Membrane Proteins Grown in Lipidic Mesophases for Structure Determination by Macromolecular Crystallography
Published on: September 2, 2012
25.8K
14:02Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
Published on: April 9, 2018
9.1K
相关概念视频
G Protein-coupled Receptors
18.7K
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...
18.7K
Gene Families
10.2K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
10.2K
