How capsaicin binds and activates nociceptor TRPV1

Time: 3:30-5:00 p.m. on Friday, July 10, 2015
Venue: 143, Life Sciences Building, Tsinghua University
Speaker: Dr. Jie Zheng

Host: Dr. Xiaodong Liu
Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously
resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflectingneither its chemical structure nor specific ligand-channel interactions. Weobtained the missing atomic-level details by iterative computation combined with systematic  site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by“pull-and-contact”interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures.

  • Wechat
  • Website

Copyright © 2014    IDG/McGovern Institute for Brain Research at Tsinghua

  • Medical Science Building D202, Tsinghua University, Beijing, China, 100084
  • +86-010-62772271