title: Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.
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.
authors.affiliation: Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA. jzheng@ucdavis.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D001665:Binding Sites; D002211:Capsaicin / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D006860:Hydrogen Bonding; D011485:Protein Binding; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin
keywords: TRPV1; capsaicin; computation; cryo-EM; ligand gating; spiciness