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bioRxiv · 10.1101/711499

Evidence that the TRPV1 S1-S4 Membrane Domain Contributes to Thermosensing

Kim, M.·Sisco, N. J.·Hilton, J. K.·Montano, C. M.·Castro, M. A.·Cherry, B. R.·Levitus, M.·Van Horn, W. D.
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Abstract

Sensing and responding to temperature is crucial in biology. The TRPV1 ion channel is a well-studied heat-sensing receptor that is also activated by vanilloid compounds including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive. The TRPV1 S1-S4 membrane domain couples chemical ligand binding to the pore domain during channel gating. However, the role of the S1-S4 domain in thermosensing is unclear. Evaluation of the isolated human TRPV1 S1-S4 domain by solution NMR, Far-UV CD, and intrinsic fluorescence shows that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity. Further NMR characterization of the temperature-dependent conformational changes suggests the contribution of the S1-S4 domain to thermosensing shares features with known coupling mechanisms between this domain with ligand and pH activation. Taken together, this study shows that the TRPV1 S1-S4 domain contributes to TRPV1 temperature-dependent activation.

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Kim, M., Sisco, N. J., Hilton, J. K., Montano, C. M., Castro, M. A., Cherry, B. R., Levitus, M., Van Horn, W. D.. 2019-07-22. Evidence that the TRPV1 S1-S4 Membrane Domain Contributes to Thermosensing. https://doi.org/10.1101/711499

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