Understand spiciness: mechanism of TRPV1 channel activation by capsaicin

Fan Yang, Jie Zheng

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel’s transmembrane segments, where it takes a “tail-up, head-down” configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by “pull-and-contact” with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalProtein and Cell
DOIs
StateAccepted/In press - Jan 2 2017

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Keywords

  • capsaicin
  • computation
  • cryo-EM
  • ligand gating
  • spiciness
  • TRPV1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

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