Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
16
01
2020
accepted:
30
07
2020
entrez:
22
8
2020
pubmed:
21
8
2020
medline:
15
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32820172
doi: 10.1038/s41467-020-18026-2
pii: 10.1038/s41467-020-18026-2
pmc: PMC7441067
doi:
Substances chimiques
TRPV Cation Channels
0
TRPV1 protein, human
0
Capsaicin
S07O44R1ZM
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4169Références
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