ArticleThe Journal of general physiology2018
A hypothetical molecular mechanism for TRPV1 activation that invokes rotation of an S6 asparagine.
Article in The Journal of general physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Functional and structural basis of a hypermorphic TRPC3 variant.Science advances · 2026Article
- Functional determinants of lysophospholipid- and voltage-dependent regulation of TRPC5 channel.Cellular and molecular life sciences : CMLS · 2024Article
- Dynamic molecular portraits of ion-conducting pores characterize functional states of TRPV channels.Communications chemistry · 2024Article
- Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels.Channels (Austin, Tex.) · 2023Article
- Temperature sensitive contact modes allosterically gate TRPV3.PLoS computational biology · 2023Article
- Real-Time Observation of Capsaicin-Induced Intracellular Domain Dynamics of TRPV1 Using the Diffracted X-ray Tracking Method.Membranes · 2023Article
- Implications of a temperature-dependent heat capacity for temperature-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An α-π transition in S6 shapes the conformational cycle of the bacterial sodium channel NavAb.The Journal of general physiology · 2023Article
- Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.International journal of molecular sciences · 2022Review
- An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing asparagine.Biophysical journal · 2022Article
- Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.Nature structural & molecular biology · 2021Article
- Structure and function of the calcium-selective TRP channel TRPV6.The Journal of physiology · 2021Review
- Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review.International journal of molecular sciences · 2021Review
- Extracellular cap domain is an essential component of the TRPV1 gating mechanism.Nature communications · 2021Article
- Article
- TRP Channels, Conformational Flexibility, and the Lipid Membrane.The Journal of membrane biology · 2020Review
- Structural insights into the gating mechanisms of TRPV channels.Cell calcium · 2020Review
- The Contribution of the Ankyrin Repeat Domain of TRPV1 as a Thermal Module.Biophysical journal · 2020Article
- Evolutionarily Conserved Interactions within the Pore Domain of Acid-Sensing Ion Channels.Biophysical journal · 2020Article
- Structural biology of thermoTRPV channels.Cell calcium · 2019Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The transient receptor potential channel vanilloid type 1 (TRPV1) is activated by a variety of endogenous and exogenous stimuli and is involved in nociception and body temperature regulation. Although the structure of TRPV1 has been experimentally determined in both the closed and open states, very little is known about its activation mechanism. In particular, the conformational changes that occur in the pore domain and result in ionic conduction have not yet been identified. Here we suggest a hypothetical molecular mechanism for TRPV1 activation, which involves rotation of a conserved asparagine in S6 from a position facing the S4-S5 linker toward the pore. This rotation is associated with hydration of the pore and dehydration of the four peripheral cavities located between each S6 and S4-S5 linker. In light of our hypothesis, we perform bioinformatics analyses of TRP and other evolutionary related ion channels, evaluate newly available structures, and reexamine previously reported water accessibility and mutagenesis experiments. These analyses provide several independent lines of evidence to support our hypothesis. Finally, we show that our proposed molecular mechanism is compatible with the prevailing theory that the selectivity filter acts as a secondary gate in TRPV1.
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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.