ArticleThe Journal of general physiology2014
Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.
Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Structural diversity of heat-sensing channel TRPV3 with Olmsted syndrome mutations.Nature communications · 2026Article
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- Article
- Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition.Nature structural & molecular biology · 2021Article
- A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TRPV4: A Physio and Pathophysiologically Significant Ion Channel.International journal of molecular sciences · 2020Review
- TRPC Channels in the SOCE Scenario.Cells · 2020Review
- Potential Novel Strategies for the Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and Beyond.Frontiers in pharmacology · 2019Review
- Store-Operated CaInternational journal of molecular sciences · 2018Review
- Article
- Article
- Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation.Proteins · 2016Article
- Temperature-sensitive gating of TRPV1 channel as probed by atomistic simulations of its trans- and juxtamembrane domains.Scientific reports · 2016Article
- Article
- Integrating TRPV1 Receptor Function with Capsaicin Psychophysics.Advances in pharmacological sciences · 2016Review
- The Integrity of the TRP Domain Is Pivotal for Correct TRPV1 Channel Gating.Biophysical journal · 2015Article
- L596-W733 bond between the start of the S4-S5 linker and the TRP box stabilizes the closed state of TRPV4 channel.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A transient receptor potential ion channel in Chlamydomonas shares key features with sensory transduction-associated TRP channels in mammals.The Plant cell · 2015Article
- Negatively charged amino acids near and in transient receptor potential (TRP) domain of TRPM4 channel are one determinant of its Ca2+ sensitivity.The Journal of biological chemistry · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transient receptor potential vanilloid receptor subtype I (TRPV1) channel acts as a polymodal sensory receptor gated by chemical and physical stimuli. Like other TRP channels, TRPV1 contains in its C terminus a short, conserved domain called the TRP box, which is necessary for channel gating. Substitution of two TRP box residues-I696 and W697-with Ala markedly affects TRPV1's response to all activating stimuli, which indicates that these two residues play a crucial role in channel gating. We systematically replaced I696 and W697 with 18 native l-amino acids (excluding cysteine) and evaluated the effect on voltage- and capsaicin-dependent gating. Mutation of I696 decreased channel activation by either voltage or capsaicin; furthermore, gating was only observed with substitution of hydrophobic amino acids. Substitution of W697 with any of the 18 amino acids abolished gating in response to depolarization alone, shifting the threshold to unreachable voltages, but not capsaicin-mediated gating. Moreover, vanilloid-activated responses of W697X mutants showed voltage-dependent gating along with a strong voltage-independent component. Analysis of the data using an allosteric model of activation indicates that mutation of I696 and W697 primarily affects the allosteric coupling constants of the ligand and voltage sensors to the channel pore. Together, our findings substantiate the notion that inter- and/or intrasubunit interactions at the level of the TRP box are critical for efficient coupling of stimulus sensing and gate opening. Perturbation of these interactions markedly reduces the efficacy and potency of the activating stimuli. Furthermore, our results identify these interactions as potential sites for pharmacological intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.