Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.

Autor: Kim M; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA.; The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA., Sisco NJ; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA.; The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA., Hilton JK; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA.; The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA., Montano CM; The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA., Castro MA; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA., Cherry BR; The Magnetic Resonance Research Center, Arizona State University, Tempe, AZ, 85287, USA., Levitus M; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA.; The Biodesign Institute Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, 85287, USA., Van Horn WD; School of Molecular Sciences, Arizona State University, 551 E. University Drive, Tempe, AZ, 85287, USA. wade.van.horn@asu.edu.; The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA. wade.van.horn@asu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Aug 20; Vol. 11 (1), pp. 4169. Date of Electronic Publication: 2020 Aug 20.
DOI: 10.1038/s41467-020-18026-2
Abstrakt: 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. Here we show that the S1-S4 domain also significantly contributes to thermosensing and couples to heat-activated gating. 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.
Databáze: MEDLINE
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