ArticleBiophysical journal2015
The Integrity of the TRP Domain Is Pivotal for Correct TRPV1 Channel Gating.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Temperature-induced structural changes in thermosensitive transient receptor potential channels (thermoTRPs).Frontiers in molecular neuroscience · 2026Review
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
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- Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases.bioRxiv : the preprint server for biology · 2024Article
- Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1.International journal of molecular sciences · 2023Article
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- Progress in the Structural Basis of thermoTRP Channel Polymodal Gating.International journal of molecular sciences · 2023Review
- TRPV1 in chronic pruritus and pain: Soft modulation as a therapeutic strategy.Frontiers in molecular neuroscience · 2022Review
- Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1.International journal of molecular sciences · 2021Article
- Identification of a helix-turn-helix motif for high temperature dependence of vanilloid receptor TRPV2.The Journal of physiology · 2021Article
- Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.Nature structural & molecular biology · 2021Article
- Mechanical Activation of MscL Revealed by a Locally Distributed Tension Molecular Dynamics Approach.Biophysical journal · 2021Article
- Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels.Scientific reports · 2020Article
- Atomistic Insights of Calmodulin Gating of Complete Ion Channels.International journal of molecular sciences · 2020Review
- Structural biology of thermoTRPV channels.Cell calcium · 2019Review
- Nociceptor Signalling through ion Channel Regulation via GPCRs.International journal of molecular sciences · 2019Review
- Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium.Nature · 2018Article
- Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.Nature structural & molecular biology · 2018Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential vanilloid subtype I (TRPV1) is a thermosensory ion channel that is also gated by chemical substances such as vanilloids. Adjacent to the channel gate, this polymodal thermoTRP channel displays a TRP domain, referred to as AD1, that plays a role in subunit association and channel gating. Previous studies have shown that swapping the AD1 in TRPV1 with the cognate from the TRPV2 channel (AD2) reduces protein expression and produces a nonfunctional chimeric channel (TRPV1-AD2). Here, we used a stepwise, sequential, cumulative site-directed mutagenesis approach, based on rebuilding the AD1 domain in the TRPV1-AD2 chimera, to unveil the minimum number of amino acids needed to restore protein expression and polymodal channel activity. Unexpectedly, we found that virtually full restitution of the AD1 sequence is required to reinstate channel expression and responses to capsaicin, temperature, and voltage. This strategy identified E692, R701, and T704 in the TRP domain as important for TRPV1 activity. Even conservative mutagenesis at these sites (E692D/R701K/T704S) impaired channel expression and abolished TRPV1 activity. However, the sole mutation of these positions in the TRPV1-AD2 chimera (D692E/K701R/S704T) was not sufficient to rescue channel gating, implying that other residues in the TRP domain are necessary to endow activity to TRPV1-AD2. A biophysical analysis of a functional chimera suggested that mutations in the TRP domain raised the energetics of channel gating by altering the coupling of stimuli sensing and pore opening. These findings indicate that inter- and/or intrasubunit interactions in the TRP domain are essential for correct TRPV1 gating.
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