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Nat Commun. 2015 Sep 30;6:8297. doi: 10.1038/ncomms9297.

A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1.

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Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
University of Chinese Academy of Sciences, Beijing 100009, China.
Department of Physiology and Membrane Biology, University of California, Davis, California 95616, USA.
Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350116, China.
Department of Molecular and Cellular Pharmacology, PKU-IDG/McGovern Institute for Brain Research, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
Department of Pharmacology, Qingdao University, Qingdao 266021, China.


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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