在TRPM子家族内保存冷却剂结合口袋
Kate Huffer1, Matthew C S Denley1, Elisabeth V Oskoui1
1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
eLife
|November 1, 2024
概括
短暂受体潜力 (TRP) 道,如TRPM8,感知寒冷. 这项研究揭示了TRPM4具有类似的冷感应口袋,由冰素调节,表明TRP通道的保护性联结结合.
科学领域:
- 分子生物学分子生物学
- 离子通道功能 离子通道功能
- 感官神经科学是一种神经科学.
背景情况:
- 短暂受体潜能 (TRP) 道是各种刺激激活的多样化的离子通道.
- TRPM8是哺乳动物有害寒冷的关键传感器.
- 通过连接体激活TRP通道的结构基础是积极研究的领域.
研究的目的:
- 调查TRPM8中的冷却剂结合口袋在其他TRPM通道亚型中的保存情况.
- 为了确定TRPM4,TRPM2和TRPM5是否共享类似的带结合口袋.
- 阐明冷却剂调节TRPM4通道活动的机制.
主要方法:
- 计算建模用于识别保存的绑定口袋.
- 电生理学记录以评估通道功能.
- 位点定向的突变发生以探测连接体结合相互作用.
主要成果:
- 一个TRPM通道的子集 (TRPM2,TRPM4,TRPM5) 具有类似于TRPM8的冷却剂结合点的口袋.
- 冷却剂冰素调节小鼠的TRPM4,增强Ca2+的灵敏度,并促进负电压下的开放.
- 影响TRPM8冷反应的突变同样改变TRPM4冰反应,表明共享的结合机制.
结论:
- TRPM4和TRPM8通道共享同类的带结合口袋.
- 这些口袋与通道孔隙开放有关.
- 这些发现表明TRPM通道家族内对联体门激活的保护机制.
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