Engineering vanilloid-sensitivity into the rat TRPV2 channel
- National Institutes of Health, United States
- Memorial Sloan Kettering Cancer Center, United States
- National Cancer Institute, United States
- University of Oxford, United Kingdom
Abstract
The TRPV1 channel is a detector of noxious stimuli, including heat, acidosis, vanilloid compounds and lipids. The gating mechanisms of the related TRPV2 channel are poorly understood because selective high affinity ligands are not available, and the threshold for heat activation is extremely high (> 50 {degree sign}C). Cryo-EM structures of TRPV1 and TRPV2 reveal that they adopt similar structures, and identify a putative vanilloid binding pocket near the internal side of TRPV1. Here we use biochemical and electrophysiological approaches to investigate the resiniferatoxin (RTx) binding site in TRPV1 and to explore the functional relationships between TRPV1 and TRPV2. Collectively, our results support the interaction of vanilloids with the proposed RTx binding pocket, and demonstrate an allosteric influence of a tarantula toxin on vanilloid binding. Moreover, we show that sensitivity to RTx can be engineered into TRPV2, demonstrating that the gating and permeation properties of this channel are similar to TRPV1.
Article and author information
Author details
Reviewing Editor
- Indira M Raman, Northwestern University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#1253-15) of the National Institute of Neurological Disorders and Stroke.
Version history
- Received: March 26, 2016
- Accepted: May 12, 2016
- Accepted Manuscript published: May 13, 2016 (version 1)
- Version of Record published: June 14, 2016 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Engineering vanilloid-sensitivity into the rat TRPV2 channel
eLife 5:e16409.
https://doi.org/10.7554/eLife.16409
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