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 e...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 simu- lation. A framework of how capsaicin binds and acti- vates TRPV1 has started to merge： capsaicin binds to a pocket formed by the channel＇s transmembrane seg- ments, where it takes a ＂tail-up, head-down＂ configu- ration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, cap- saicin stabilizes the open state of TRPV1 by ＂pull-and- contact＂ with the $4-$5 linker. Understanding the ligand-host interaction will greatly facilitate pharma- ceutical efforts to develop novel analgesics targeting TRPV1.展开更多
文摘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 simu- lation. A framework of how capsaicin binds and acti- vates TRPV1 has started to merge： capsaicin binds to a pocket formed by the channel＇s transmembrane seg- ments, where it takes a ＂tail-up, head-down＂ configu- ration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, cap- saicin stabilizes the open state of TRPV1 by ＂pull-and- contact＂ with the $4-$5 linker. Understanding the ligand-host interaction will greatly facilitate pharma- ceutical efforts to develop novel analgesics targeting TRPV1.
