与G蛋白结合的受体:对微生物代谢物的目标,以及与微生物群-免疫-大脑相互作用的机械联系
Gajender Aleti1,2, Emily A Troyer2, Suzi Hong2,3
1Department of Food and Animal Sciences, Tennessee State University, Nashville, TN, 37209, USA.
Brain, behavior, & immunity - health
|August 10, 2023
概括
肠道微生物产生小分子,与人类G蛋白结合受体 (GPCRs) 相互作用,影响健康. 这项研究绘制了这些微生物代谢物及其相互作用的地图,揭示了肠-免疫-大脑轴的潜在治疗点.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类健康受到微生物相互作用的显著影响,但分子机制尚未完全理解.
- 由肠道微生物群产生的小分子可以作为人类G蛋白合受体 (GPCR) 的配体,调节生理功能并提供对微生物与人类相互作用的见解.
- 了解这些跨王国分子通信对于破译健康和疾病状态至关重要.
研究的目的:
- 分析已知的结合GPCRs并激活下游信号通路的细菌代谢物.
- 用代谢学数据绘制人体部位中这些代谢物的分布图,并将它们与健康状况联系起来.
- 确定GPCR介导的关键微生物代谢物与人类细胞的相互作用,特别是调节肠-免疫-大脑轴的相互作用.
主要方法:
- 对与GPCRs结合并激活信号通路的细菌代谢物的分析.
- 使用基于公共质谱的代谢学数据绘制代谢物分布图.
- 集成与RNA-Seq表达和GPCR定位数据从人类蛋白质地图.
- 对小分子吸收和血脑屏障透性的评估.
主要成果:
- 推断主要的GPCR介导的微生物代谢物-人类细胞相互作用,控制肠-免疫-大脑轴.
- 确定了小分子与人类细胞受体在肠道,免疫和神经系统细胞上的特定分子相互作用.
- 证明了这些微生物代谢物的临床翻译潜力.
- 提供了一个开源资源,用于在可服药的人类GPCRome中查询生物活性分子.
结论:
- 与GPCRs相互作用的微生物代谢物代表了肠-免疫-大脑轴调节的关键接口.
- 这些相互作用为治疗干预提供了有希望的途径.
- 开发的框架促进了微生物组,代谢学和机理学研究的整合,以改善理解和治疗策略.
相关概念视频
G Protein-coupled Receptors
12.3K
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...
12.3K
G-protein Coupled Receptors
120.3K
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.
120.3K
Transducer Mechanism: G Protein–Coupled Receptors
2.1K
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,...
GPCRs are also called heptahelical,...
2.1K
GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Microorganisms in Medicine and Therapeutics
54
Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
54
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K


