Multimodal Gating Mechanisms of TRPV1 Ion Channels

TRPV1 离子通道的多模态门控机制

• 批准号: 10082453
• 负责人: Sharona E Gordon
• 金额: $ 41.99万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082453
• 关键词: Agonist; Amino Acids; Binding; Biological; Capsaicin; Cells; Computing Methodologies; Coupled; Coupling; Data; Development; Fluorescence Resonance Energy Transfer; Goals; Ion Channel; Ions; Libraries; Ligands; Light; Lipids; Measurement; Measures; Membrane; Membrane Proteins; Metal Binding Site; Methods; Modality; Modeling; Molecular; Molecular Conformation; Nature; Pain; Pain management; Phosphatidylinositol 4,5-Diphosphate; Positioning Attribute; Protein Engineering; Protons; Publishing; Quality of life; Savory; Side; Signal Transduction; Stimulus; Structure; System; TRPV1 gene; Temperature; Testing; Time; Toxin; Transition Elements; anandamide; base; capsazepine; chemical property; chronic pain; clinically relevant; experimental study; extracellular; improved; innovation; maltose-binding protein; multimodality; non-opioid analgesic; novel; novel strategies; pain receptor; physical property; side effect; tool

Project summary The goal of this proposal is to determine the molecular mechanisms underlying multi-modal gating of the pain-receptor ion channel TRPV1 by interrogating the structural mechanisms for activation by capsaicin, heat, protons, savory compounds, and signaling lipids. We will use tmFRET and computational methods to determine the conformational change induced by each modality and the coupling between modalities.

项目总结 这项建议的目标是确定潜在的多模式门的分子机制 痛觉受体离子通道TRPV1激活的结构机制 辣椒素、辣味、质子、可口化合物和信号脂质。我们将使用tmFRET和 计算方法来确定每种形态引起的构象变化和 医疗模式之间的耦合。