Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.
10.1007/s13238-016-0353-7
- Author:
Fan YANG
1
;
Jie ZHENG
2
Author Information
1. Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA.
2. Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA. jzheng@ucdavis.edu.
- Publication Type:Journal Article
- Keywords:
TRPV1;
capsaicin;
computation;
cryo-EM;
ligand gating;
spiciness
- MeSH:
Binding Sites;
Capsaicin;
chemistry;
pharmacokinetics;
Humans;
Hydrogen Bonding;
Protein Binding;
TRPV Cation Channels;
chemistry;
genetics;
metabolism
- From:
Protein & Cell
2017;8(3):169-177
- CountryChina
- Language:English
-
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.
