诺西塞/孤儿素FQ受体与模仿性的复合体中的结构
Aaron A Thompson1, Wei Liu, Eugene Chun
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Nature
|May 19, 2012
概括
诺西/孤儿素FQ受体 (NOP) 的晶体结构揭示了连接体结合的原子细节. 这个结构解释了NOP的结构.
科学领域:
- 结构生物学是结构生物学.
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 包括经典的delta,kappa和微型亚型在内的阿片类受体对于疼痛信号至关重要.
- 后来确定了诺西/孤儿素FQ受体 (NOP),这是一个独特的阿片类受体家族成员,具有独特的药理学.
- NOP与经典阿片类受体具有序列相似性,但在配体选择性上有显著差异.
研究的目的:
- 为了确定人类NOP受体的晶体结构.
- 阐明在NOP受体上对联体的识别和选择性的原子细节.
- 为了解NOP独特的药理特征提供结构基础.
主要方法:
- 使用X射线晶体学来解决人类NOP的结构.
- 结构被确定为复杂的与模仿性对手,化合物-24 (C-24).
- 对NOP和经典阿片类受体 (kappa和micro) 之间的结构差异进行了比较分析.
主要成果:
- 确定了与化合物-24复合的人类NOP的晶体结构.
- 揭示了化合物-24如何与NOP受体相互作用的原子细节.
- 在NOP和古典阿片类受体之间,在带结合口袋中发现了显著的形状差异.
- 这些结构变异解释了NOP对联体的独特选择性.
结论:
- NOP-化合物-24结构为NOP受体功能和连接体选择性提供了原子洞察力.
- 与经典阿片类受体相比,NOP的独特药理学的原因在于结合口袋中的结构差异.
- 这种结构模板对于新型NOP受体连接体的合理设计是有价值的.
更多相关视频
09:09Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
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
相关概念视频
Nociception
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...
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...
Drug-Receptor Interaction: Agonist
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
The Two-State Receptor Model
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
The binding affinity of a drug determines its interaction with one...
Cholinergic Receptors: Nicotinic
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
