AuPS Logo Programme
Previous Next PDF

Heat sensation of temperature sensitive TRPV1 channel supported by the transmembrane core domain

L. Ma,1,2 F. Yang,2 Y. Cui,2,3 X. Cao,2,3 K. Wang3,4 and J. Zheng,2 1Institute for Molecular Bioscience, The University of Queensland, Brisbane, St Lucia, QLD 4072, Australia, 2Department of Physiology and Membrane Biology, University of California, Davis, CA 95616, USA, 3Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China and 44PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.

Several transient receptor potential vanilloid (TRPV) channels serve as molecular temperature sensors. However, the structural basis for their high-sensitivity heat activation is strongly debated. Inspired by the recent finding of intrinsic high temperature sensitivity in homologous voltage-gated potassium channels (Kv), here we investigated this issue using two complementary strategies, unstructured peptide-insertion screening (UPS) and chimera screening. We showed that the transmembrane (TM) S1-S6 region of TRPV1 is sufficient to support heat activation, while both N and C termini contribute to this process. Furthermore, within the TM region, the pore domain plays a central role in determining the heat activation process; swapping the pore-forming region of TRPV1 with TRPV2 and TRPV3 could transfer distinct heat activation properties among these channels.