ArticleProceedings of the National Academy of Sciences of the United States of America2019
Human mutations highlight an intersubunit cation-π bond that stabilizes the closed but not open or inactivated states of TRPV channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Inactivation Switch for Run-up in TRPV2.Research square · 2026Article
- Thermodynamic coupling between cold and heat activations of TRPV2.Scientific reports · 2026Article
- Temperature-dependent gating pathways in TRPV3.Scientific reports · 2026Article
- Thermoring basis for the proton-driven heat activation of a cation-selective channel in myriapods.Scientific reports · 2025Article
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
- TRPV4-dependent CaBiophysical journal · 2024Article
- TRPV4 mutations causing mixed neuropathy and skeletal phenotypes result in severe gain of function.Annals of clinical and translational neurology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
An adequate response of a living cell to the ever-changing environment requires integration of numerous sensory inputs. In many cases, it can be achieved even at the level of a single receptor molecule. Polymodal transient receptor potential (TRP) channels have been shown to integrate mechanical, chemical, electric, and thermal stimuli. Inappropriate gating can lead to pathologies. Among the >60 known TRP vanilloid subfamily (V) 4 mutations that interfere with bone development are Y602C or R616Q at the S4-S5 linker. A cation-π bond between the conservative residues Y602 and R616 of neighboring subunits appears likely in many homologous channel structures in a closed state. Our experiments with TRPV4 mutants indicate that the resting-closed state remains stable while the bond is substituted by a salt bridge or disulfide bond, whereas disruption of the contact by mutations like Y602C or R616Q produces gain-of-function phenotypes when TRPV4 is heterologously expressed in the
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Registered trials
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