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标题：Heat activation is intrinsic to the pore domain of TRPV1
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作者：Feng Zhang ; Andres Jara-Oseguera ; Tsg-Hui Chang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：2
页码：E317-E324
DOI：10.1073/pnas.1717192115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The TRPV1 channel is a sensitive detector of pain-producing stimuli, including noxious heat, acid, inflammatory mediators, and vanilloid compounds. Although binding sites for some activators have been identified, the location of the temperature sensor remains elusive. Using available structures of TRPV1 and voltage-activated potassium channels, we engineered chimeras wherein transmembrane regions of TRPV1 were transplanted into the Shaker Kv channel. Here we show that transplanting the pore domain of TRPV1 into Shaker gives rise to functional channels that can be activated by a TRPV1-selective tarantula toxin that binds to the outer pore of the channel. This pore-domain chimera is permeable to Na⁺, K⁺, and Ca²⁺ ions, and remarkably, is also robustly activated by noxious heat. Our results demonstrate that the pore of TRPV1 is a transportable domain that contains the structural elements sufficient for activation by noxious heat.
关键词：capsaicin ; transient receptor potential ; thermosensing ; tarantula toxin ; DkTx