人体上皮质通道TRPV6的开放
Luke L McGoldrick1,2, Appu K Singh1, Kei Saotome1
1Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, New York 10032, USA.
Nature
|December 21, 2017
概括
暂时受体潜在化物亚家族成员6 (TRPV6) 通道调节的吸收. 新的冷EM结构揭示了一种独特的关门机制,涉及S6中的α-to-pi螺旋过渡,解释了构成性活动和疾病相关性.
科学领域:
- 结构生物学 结构生物学
- 离子通道生理学 离子通道生理学
- 生物物理学的生物物理.
背景情况:
- 选择性的过渡受体潜在类子家族成员6 (TRPV6) 通道对于上皮细胞中的吸收至关重要.
- TRPV6的失调与包括癌症在内的各种疾病有关.
- 之前的研究解决了封闭状态结构,但封闭机制仍然难以捉摸.
研究的目的:
- 阐明TRPV6通道门的结构基础 (打开和关闭).
- 了解TRPV6通道如何在离子透的开放和关闭状态之间过渡.
- 为 TRPV6 频道的构成性活动提供见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定人类TRPV6.6的高分辨率结构.
- 对于通道的开放状态和封闭状态都获得了结构.
- 分析的重点是孔隙层跨膜螺旋体S6.6的构造变化.
主要成果:
- 在开放和关闭状态之间,选择性过器的形状保持不变,这突出了其在离子透中的作用.
- 通道开通涉及S6螺旋在氨酸链上的α-to-pi螺旋转变.
- 这种过渡导致S6螺旋曲和旋转,改变了孔隙的可访问性.
结论:
- 已经确定了TRPV6通道的独特关门机制,涉及S6螺旋过渡.
- 这种机制解释了TRPV6频道的构成性活动.
- 这些发现为TRPV6在生理学和疾病中的功能提供了结构性的见解.
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