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 language | English (US) |
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Pages (from-to) | 1-9 |
Number of pages | 9 |
Journal | Protein and Cell |
DOIs | |
State | Accepted/In press - Jan 2 2017 |
Keywords
- capsaicin
- computation
- cryo-EM
- ligand gating
- spiciness
- TRPV1
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Drug Discovery
- Cell Biology