血清素5-HT3受体的形态转变
Lucie Polovinkin1, Ghérici Hassaine2, Jonathan Perot1
1CNRS, Université Grenoble Alpes, CEA, IBS, Grenoble, France.
Nature
|November 8, 2018
概括
研究人员可视化了5-HT3受体, 这些结构以史无前例的细节捕捉了连体结合和形状变化.
科学领域:
- 神经科学
- 结构生物学
- 生物化学
背景情况:
- 血清素5-HT3受体是对神经传递至关重要的氨基联接离子通道 (pLGIC).
- 它是治疗吐,恶心,刺激性肠综合征和抑郁症等疾病的目标.
- 了解pLGIC在道关口中的构造转换仍然是一个挑战.
研究的目的:
- 阐明小鼠5-HT3受体的形状转换和封闭机制.
- 以原子分辨率可视化连接物结合.
- 提供对受体动力学和离子透的计算见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定5-HT3受体的结构.
- 结构与热,血清素和正调节剂复合得到.
- 使用计算方法分析动力学,孔隙水分和自由能量概况.
主要成果:
- 确定了小鼠5-HT3受体的四个冷EM结构,分辨率为3. 24. 5 Å.
- 结构捕获了不同的状态,包括热结合,结合和开放状态.
- 计算分析提供了关于门运动,孔隙水分和阴离子可访问性的见解.
结论:
- 这项研究提供了前所未有的结构细节,说明了5-HT3受体的结合和构造变化.
- 这些发现加深了对PLGIC门机制的理解.
- 高分辨率结构为未来针对5-HT3受体的药物开发提供了基础.
相关概念视频
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
985
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
985
Conformity
48.2K
Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
48.2K
Cooperative Allosteric Transitions
8.7K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.7K
Phase Transitions
23.2K
Whether solid, liquid, or gas, a substance's state depends on the order and arrangement of its particles (atoms, molecules, or ions). Particles in the solid pack closely together, generally in a pattern. The particles vibrate about their fixed positions but do not move or squeeze past their neighbors. In liquids, although the particles are closely spaced, they are randomly arranged. The position of the particles are not fixed—that is, they are free to move past their neighbors to...
23.2K
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
668
5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
668
Internal Receptors
74.7K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.7K


