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

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Aug 22

PMID 32820172

Citations 18

Authors

Minjoo Kim

Nicholas J Sisco

Jacob K Hilton

Camila M Montano

Manuel A Castro

Brian R Cherry

Marcia Levitus

Wade D Van Horn

Affiliations

Soon will be listed here.

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. 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.

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