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) |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Protein and Cell |
| DOIs | |
| State | Accepted/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
Cite this
Understand spiciness : mechanism of TRPV1 channel activation by capsaicin. / Yang, Fan; Zheng, Jie.
In: Protein and Cell, 02.01.2017, p. 1-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Understand spiciness
T2 - mechanism of TRPV1 channel activation by capsaicin
AU - Yang, Fan
AU - Zheng, Jie
PY - 2017/1/2
Y1 - 2017/1/2
N2 - 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.
AB - 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.
KW - capsaicin
KW - computation
KW - cryo-EM
KW - ligand gating
KW - spiciness
KW - TRPV1
UR - http://www.scopus.com/inward/record.url?scp=85007589336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007589336&partnerID=8YFLogxK
U2 - 10.1007/s13238-016-0353-7
DO - 10.1007/s13238-016-0353-7
M3 - Article
C2 - 28044278
AN - SCOPUS:85007589336
SP - 1
EP - 9
JO - Protein and Cell
JF - Protein and Cell
SN - 1674-800X
ER -