在TRPM子家族内保存冷却剂结合口袋
Kate Huffer1, Matthew C S Denley1, Elisabeth V Oskoui1,2
1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
bioRxiv : the preprint server for biology
|June 3, 2024
概括
短暂的受体潜力 (TRP) 道,如TRPM8,感知寒冷. 研究人员在TRPM4,TRPM2和TRPM5中发现了类似的冷却剂结合口袋,揭示了道激活的保存机制.
科学领域:
- 分子生物学分子生物学
- 离子通道生物物理学
- 计算建模计算建模
背景情况:
- 短暂受体潜能 (TRP) 通道是由各种刺激激活的关键离子通道.
- 尽管具有多种功能,但TRP通道结构显示了保留的跨膜域.
- TRPM8是一种有害寒冷的哺乳动物传感器,由冷却剂激活.
研究的目的:
- 研究TRPM8中的冷却剂结合口袋在其他TRPM通道子类型中的保存情况.
- 阐明这种保存口袋在其他TRPM通道的功能中的作用.
主要方法:
- 对TRP通道结构的计算分析.
- 电生理学记录以评估通道活动.
- 位点定向的突变发生以探测连接体的结合和激活.
主要成果:
- 在TRPM2,TRPM4和TRPM5频道中发现了一种类似于TRPM8的保存冷却剂结合口袋.
- 冷却剂冰素通过增强Ca2+敏感性和改变电压依赖性来调节TRPM4活动.
- 影响TRPM8冷却剂结合的突变同样影响了冰素对TRPM4的影响.
结论:
- TRPM4和TRPM8共享同类的连接体结合口袋.
- 这些口袋与通道孔隙开放有关.
- 保存的结构元素在TRP通道中介于依赖联体的激活.
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