TRP channel activation by reversible covalent modification

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 51 - Trang 19564-19568 - 2006
A. Scott Hinman1, Huai-hu Chuang1, Diana M. Bautista1, David Julius1
1Departments of Physiology and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158

Tóm tắt

Allyl isothiocyanate, the pungent principle of wasabi and other mustard oils, produces pain by activating TRPA1, an excitatory ion channel on sensory nerve endings. Isothiocyanates are membrane-permeable electrophiles that form adducts with thiols and primary amines, suggesting that covalent modification, rather than classical lock-and-key binding, accounts for their agonist properties. Indeed, we show that thiol reactive compounds of diverse structure activate TRPA1 in a manner that relies on covalent modification of cysteine residues within the cytoplasmic N terminus of the channel. These findings suggest an unusual paradigm whereby natural products activate a receptor through direct, reversible, and covalent protein modification.

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Tài liệu tham khảo

10.1016/S0959-4388(03)00101-6

10.1146/annurev.physiol.68.040204.100431

10.1038/nature02282

10.1016/S0896-6273(04)00150-3

10.1073/pnas.0505356102

10.1016/j.cub.2005.04.018

10.1016/j.cell.2006.02.023

M Smith, J March, J March March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (Wiley, New York, 2001).

10.1016/S0223-5234(03)00141-7

10.1055/s-2001-9752

10.1021/tx010029w

10.1016/S0896-6273(00)80564-4

10.1016/j.neuron.2004.08.038

10.1038/nchembio0705-85

10.1110/ps.03554604

10.1038/nature03066

10.1038/nature04437

10.1016/j.cub.2004.02.050

10.1093/emboj/cdf651

10.1016/S0896-6273(00)80055-0

10.1038/71090

10.1126/science.279.5348.234

10.1038/nrm1569

10.1038/nchembio821

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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 51

19564-19568

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