Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel
Open accessPublished version of a preprint
Abstract
Mechanically activating (MA) channels transduce numerous physiological functions. Tentonin 3/TMEM150C (TTN3) confers MA currents with slow inactivation kinetics in somato- and barosensory neurons. However, questions were raised about its role as a Piezo1 regulator and its potential as a channel pore. Here, we demonstrate that purified TTN3 proteins incorporated into the lipid bilayer displayed spontaneous and pressure-sensitive channel currents. These MA currents were conserved across vertebrates and differ from Piezo1 in activation threshold and pharmacological response. Deep neural network structure prediction programs coupled with mutagenetic analysis predicted a rectangular-shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit center. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These findings suggest that TTN3 is a pore-forming subunit of a distinct slow inactivation MA channel, potentially possessing a tetrameric structure.
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Cites
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“In addition, we utilized deep learning methods to achieve prediction accuracies greater than those of force-field-based approaches 21–23 to gain structural insight into TTN3 action.”
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- Authors
- Pak, S., Ryu, H., Lim, S., Nguyen, T.-L., Yang, S., Kang, S., Yu, Y. G., Woo, J., Kim, C., Fenollar-Ferrer, C., Wood, J. N., Lee, M.-O., Hong, G.-S., Han, K., Kim, T. S., & Oh, U.
- Affiliations
- Seoul National University (KR)
- Korea Institute of Science and Technology (KR)
- Kookmin University (KR)
- University College London (GB)
- Seoul National University of Science and Technology (KR)
- Corresponding author
- Hong, Gyu-Sang
- Han, Kyungreem
- Kim, Tae Song
- Oh, Uhtaek
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 43
- Issue
- 6
- Pages
- 114334
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC11310380
- OpenAlex
- W4399418647
- Cited by
- 6
- References
- 6
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NIDCD (DC000039)
- KIST (2E32231, 2Z06588)
- Palm Healthcare Foundation
- National Research Foundation of Korea (NRF- 2020R1A3A300192913, NRF-2020R1C1C101024513, RS-2023-00254795, NRF-2022M3E5E801739512, 2020R1A2C210036313, 2020R1A2C1101174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Keywords
- mechanosensitive ion channels, slow inactivation, pore-forming subunit, Piezo1, somatosensory neurons, transmembrane helices, mutagenesis
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Ion Channels, Lipid Bilayers, Membrane Proteins, Mutation, Protein Subunits, Mechanotransduction, Cellular, Mice, HEK293 Cells
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