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Structural biology of thermoTRPV channels.
Cell Calcium ( IF 4.3 ) Pub Date : 2019-11-01 , DOI: 10.1016/j.ceca.2019.102106 Peng Yuan 1
Cell Calcium ( IF 4.3 ) Pub Date : 2019-11-01 , DOI: 10.1016/j.ceca.2019.102106 Peng Yuan 1
Affiliation
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Essential for physiology, transient receptor potential (TRP) channels constitute a large and diverse family of cation channels functioning as cellular sensors responding to a vast array of physical and chemical stimuli. Detailed understanding of the inner workings of TRP channels has been hampered by a lack of atomic structures, though structural biology of TRP channels has been an enthusiastic endeavor since their molecular identification two decades ago. These multi-domain integral membrane proteins, exhibiting complex polymodal gating behavior, have been a challenge for traditional X-ray crystallography, which requires formation of well-ordered protein crystals. X-ray structures remain limited to a few TRP channel proteins to date. Fortunately, recent breakthroughs in single-particle cryo-electron microscopy (cryo-EM) have enabled rapid growth of the number of TRP channel structures, providing tremendous insights into channel gating and regulation mechanisms and serving as foundations for further mechanistic investigations. This brief review focuses on recent exciting developments in structural biology of a subset of TRP channels, the calcium-permeable, non-selective and thermosensitive vanilloid subfamily of TRP channels (TRPV1-4), and the permeation and gating mechanisms revealed by structures.
中文翻译：
thermoTRPV通道的结构生物学。
对于生理至关重要，瞬态受体电位（TRP）通道构成了一个庞大而多样的阳离子通道家族，起着对大量物理和化学刺激做出响应的细胞传感器的作用。缺乏原子结构阻碍了对TRP通道内部运作的详细了解，尽管自20年前对TRP通道进行分子鉴定以来，其结构生物学一直是一项积极的工作。这些多域整体膜蛋白，表现出复杂的多峰门控行为，已经成为传统X射线晶体学的一个挑战，传统X射线晶体学要求形成有序的蛋白质晶体。迄今为止，X射线结构仍局限于少数TRP通道蛋白。幸运的是，单粒子冷冻电子显微镜（cryo-EM）的最新突破使TRP通道结构的数量迅速增长，为通道门控和调节机制提供了深刻的见识，并为进一步的机械研究奠定了基础。这篇简短的综述关注于TRP通道子集的结构生物学，TRP通道的钙可渗透，非选择性和热敏性香草类亚家族（TRPV1-4）的近期激动人心的发展，以及结构揭示的渗透和门控机制。
更新日期：2019-11-01
中文翻译：
thermoTRPV通道的结构生物学。
对于生理至关重要，瞬态受体电位（TRP）通道构成了一个庞大而多样的阳离子通道家族，起着对大量物理和化学刺激做出响应的细胞传感器的作用。缺乏原子结构阻碍了对TRP通道内部运作的详细了解，尽管自20年前对TRP通道进行分子鉴定以来，其结构生物学一直是一项积极的工作。这些多域整体膜蛋白，表现出复杂的多峰门控行为，已经成为传统X射线晶体学的一个挑战，传统X射线晶体学要求形成有序的蛋白质晶体。迄今为止，X射线结构仍局限于少数TRP通道蛋白。幸运的是，单粒子冷冻电子显微镜（cryo-EM）的最新突破使TRP通道结构的数量迅速增长，为通道门控和调节机制提供了深刻的见识，并为进一步的机械研究奠定了基础。这篇简短的综述关注于TRP通道子集的结构生物学，TRP通道的钙可渗透，非选择性和热敏性香草类亚家族（TRPV1-4）的近期激动人心的发展，以及结构揭示的渗透和门控机制。
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