孤儿G蛋白结合受体:正在寻找一个家庭的持续搜索
Amie Jobe1, Ranjit Vijayan1,2,3
1Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Frontiers in pharmacology
|March 18, 2024
概括
研究人员正在推进对孤儿G蛋白结合受体 (GPCRs) 的配体的鉴定. 机器学习有助于预测连接体,这对于理解这些重要的跨膜受体至关重要.
科学领域:
- 生物化学和分子生物学
- 药理学 药理学是指药理学的学科.
- 基因组学就是基因组学.
背景情况:
- G蛋白结合受体 (GPCR) 是最大的受体超级家族,占人类蛋白质编码基因的4%.
- 很大一部分这些跨膜受体被归类为"孤儿受体",因为没有已识别的内源性连接体.
- 反向药理学方法在历史上一直用于孤儿受体的表征,尽管GPCR信号复杂性存在挑战.
研究的目的:
- 为应对识别孤儿GPCRs内源配体的挑战.
- 为了探索GPCRs的deorphanization的先进的方法,考虑到他们的治疗意义.
- 突出孤儿GPCR连体发现的进展和未来方向.
主要方法:
- 利用机器学习方法进行准确的连接体预测.
- 利用计算方法的进步来克服结构数据的局限性.
- 在寻找原生配体时应用反向药理学原理.
主要成果:
- 尽管3D结构数据有限,但在使用机器学习预测GPCR配体方面取得了显著进展.
- 配体稀缺仍然是孤儿GPCRs脱的主要障碍.
- 计算方法在加速识别潜在的GPCR配体方面被证明是有价值的.
结论:
- 由于其治疗相关性,对本地孤儿GPCR配体的搜索正在进行中.
- 对于孤儿GPCR脱的未来策略应该是全面的,承认GPCR信号的细微性质.
- 综合计算和实验方法的多方面的方法对于充分描述剩余的孤儿GPCRs至关重要.
相关概念视频
G Protein-coupled Receptors
12.0K
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...
12.0K
Transducer Mechanism: G Protein–Coupled Receptors
2.0K
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,...
2.0K
G-protein Coupled Receptors
118.7K
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.
118.7K
GPCR Desensitization
6.0K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.0K
Assembly of Signaling Complexes
5.8K
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,...
5.8K
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


