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

Minjoo Kim, Nicholas J. Sisco, Jacob K. Hilton, Camila M. Montano, Manuel A. Castro, Brian R. Cherry, Marcia Levitus, Wade D. Van Horn

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Article number4169
JournalNature communications
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing'. Together they form a unique fingerprint.

Cite this