Abstract：
The transient receptor potential ion channel TRPA1 is a Ca2+-permeable nonselective cation channel widely expressed in sensory neurons, but also in many nonneuronal tissues typically possessing barrier functions, such as the skin, joint synoviocytes, cornea, and the respiratory and intestinal tracts. Here, the primary role of TRPA1 is to detect potential danger stimuli that may threaten the tissue homeostasis and the health of the organism. The ability to directly recognize signals of different modalities, including chemical irritants, extreme temperatures, or osmotic changes resides in the characteristic properties of the ion channel protein complex. Recent advances in cryo-electron microscopy have provided an important framework for understanding the molecular basis of TRPA1 function and have suggested novel directions in the search for its pharmacological regulation. This chapter summarizes the current knowledge of human TRPA1 from a structural and functional perspective and discusses the complex allosteric mechanisms of activation and modulation that play important roles under physiological or pathophysiological conditions. In this context, major challenges for future research on TRPA1 are outlined.
摘要：
瞬时受体电位离子通道TRPA1是在感觉神经元中广泛表达的Ca2+渗透性非选择性阳离子通道,但在许多通常具有屏障功能的非神经元组织中，比如皮肤，关节滑膜细胞，角膜,以及呼吸道和肠道。这里,TRPA1的主要作用是检测可能威胁组织稳态和生物体健康的潜在危险刺激。能够直接识别不同模态的信号，包括化学刺激物,极端温度,或渗透变化在于离子通道蛋白复合物的特征特性。低温电子显微镜的最新进展为理解TRPA1功能的分子基础提供了重要的框架，并为寻找其药理调控提供了新的方向。本章从结构和功能角度总结了人类TRPA1的最新知识，并讨论了在生理或病理生理条件下发挥重要作用的激活和调节的复杂变构机制。在这种情况下，概述了TRPA1未来研究的主要挑战。
