Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9297
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Funding
- Ministry of Science and Technology of China [2013CB911300, 2010CB529800, 2013CB531302]
- National Science Foundation of China [31025025, U1132601, 31200590, 31370741]
- Chinese Academy of Sciences [KSZD-EW-Z-007]
- Yunnan Province [2011CI139, 2012BC009]
- Ministry of Education of China
- 111 Project [B07001]
- National Institutes of Health [R01NS072377]
- American Heart Association [14POST19820027]
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The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds to heat with exquisite sensitivity through an unknown mechanism. Here we report the identification of a novel toxin, RhTx, from the venom of the Chinese red-headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx is a 27-amino-acid small peptide that forms a compact polarized molecule with very rapid binding kinetics and high affinity for TRPV1. We show that RhTx targets the channel's heat activation machinery to cause powerful heat activation at body temperature. The RhTx-TRPV1 interaction is mediated by the toxin's highly charged C terminus, which associates tightly to the charge-rich outer pore region of the channel where it can directly interact with the pore helix and turret. These findings demonstrate that RhTx binding to the outer pore can induce TRPV1 heat activation, therefore providing crucial new structural information on the heat activation machinery.
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