Engineering vanilloid-sensitivity into the rat TRPV2 channel

Engineering vanilloid-sensitivity into the rat TRPV2 channel

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 (&...

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Main Authors: Zhang, Feng, Hanson, Sonya M, Jara-Oseguera, Andres, Krepkiy, Dmitriy, Bae, Chanhyung, Pearce, Larry V, Blumberg, Peter M, Newstead, Simon, Swartz, Kenton J
Format: Online
Language:English
Published: eLife Sciences Publications, Ltd 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907692/
id pubmed-4907692
recordtype oai_dc
spelling pubmed-49076922016-06-15 Engineering vanilloid-sensitivity into the rat TRPV2 channel Zhang, Feng Hanson, Sonya M Jara-Oseguera, Andres Krepkiy, Dmitriy Bae, Chanhyung Pearce, Larry V Blumberg, Peter M Newstead, Simon Swartz, Kenton J Biophysics and Structural Biology 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°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. eLife Sciences Publications, Ltd 2016-05-13 /pmc/articles/PMC4907692/ /pubmed/27177419 http://dx.doi.org/10.7554/eLife.16409 Text en http://creativecommons.org/publicdomain/zero/1.0/ 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 (http://creativecommons.org/publicdomain/zero/1.0/) .
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Feng
Hanson, Sonya M
Jara-Oseguera, Andres
Krepkiy, Dmitriy
Bae, Chanhyung
Pearce, Larry V
Blumberg, Peter M
Newstead, Simon
Swartz, Kenton J
spellingShingle Zhang, Feng
Hanson, Sonya M
Jara-Oseguera, Andres
Krepkiy, Dmitriy
Bae, Chanhyung
Pearce, Larry V
Blumberg, Peter M
Newstead, Simon
Swartz, Kenton J
Engineering vanilloid-sensitivity into the rat TRPV2 channel
author_facet Zhang, Feng
Hanson, Sonya M
Jara-Oseguera, Andres
Krepkiy, Dmitriy
Bae, Chanhyung
Pearce, Larry V
Blumberg, Peter M
Newstead, Simon
Swartz, Kenton J
author_sort Zhang, Feng
title Engineering vanilloid-sensitivity into the rat TRPV2 channel
title_short Engineering vanilloid-sensitivity into the rat TRPV2 channel
title_full Engineering vanilloid-sensitivity into the rat TRPV2 channel
title_fullStr Engineering vanilloid-sensitivity into the rat TRPV2 channel
title_full_unstemmed Engineering vanilloid-sensitivity into the rat TRPV2 channel
title_sort engineering vanilloid-sensitivity into the rat trpv2 channel
description 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°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.
publisher eLife Sciences Publications, Ltd
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907692/
_version_ 1613594624729808896

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