CTD公司
生物物理学
门控
冷敏
电生理学
化学
双层
离子通道
生物化学
生物
膜
受体
神经科学
基因
海洋学
地质学
突变体
作者
Lavanya Moparthi,Viktor Sinica,Vamsi K. Moparthi,Mohamed Kreir,Thibaut Vignane,Miloš R. Filipović,Viktorie Vlachová,Peter M. Zygmunt
标识
DOI:10.1038/s41467-022-33876-8
摘要
Abstract TRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, ∆1–688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas ∆1–854 hTRPA1, also lacking the S1–S4 voltage sensing-like domain (VSLD), gained sensitivity to cold but lost its heat sensitivity. In hTRPA1 intrinsic tryptophan fluorescence studies, cold and heat evoked rearrangement of VSLD and the C-terminus domain distal to the transmembrane pore domain S5–S6 (CTD). In whole-cell electrophysiology experiments, replacement of the CTD located cysteines 1021 and 1025 with alanine modulated hTRPA1 cold responses. It is proposed that hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5–S6 pore region and the VSLD, respectively.
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