Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel

Sungmin Pak; Hyunil Ryu; Sujin Lim; Thien-Luan Nguyen; Sungwook Yang; Sumin Kang; Yeon Gyu Yu; Junhyuk Woo; Chanjin Kim; Cristina Fenollar-Ferrer; John N. Wood; Mi-Ock Lee; Gyu-Sang Hong; Kyungreem Han; Tae Song Kim; Uhtaek Oh

Cell Reports (Jun 2024)

Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel

Sungmin Pak,
Hyunil Ryu,
Sujin Lim,
Thien-Luan Nguyen,
Sungwook Yang,
Sumin Kang,
Yeon Gyu Yu,
Junhyuk Woo,
Chanjin Kim,
Cristina Fenollar-Ferrer,
John N. Wood,
Mi-Ock Lee,
Gyu-Sang Hong,
Kyungreem Han,
Tae Song Kim,
Uhtaek Oh

Affiliations

Sungmin Pak: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; College of Pharmacy, Seoul National University, Seoul 08826, Korea
Hyunil Ryu: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea
Sujin Lim: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea
Thien-Luan Nguyen: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; College of Pharmacy, Seoul National University, Seoul 08826, Korea
Sungwook Yang: Artificial Intelligence and Robotics Institute, KIST, Seoul 02792, Korea
Sumin Kang: Department of Chemistry, Kookmin University, Seoul 02707, Korea
Yeon Gyu Yu: Department of Chemistry, Kookmin University, Seoul 02707, Korea
Junhyuk Woo: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea
Chanjin Kim: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea
Cristina Fenollar-Ferrer: Stiles-Nicholson Brain Institute at Florida Atlantic University, Jupiter, FL 33458, USA; Laboratory of Molecular Genetics, NIDCD, NIH, Bethesda, MD 20892, USA
John N. Wood: Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK
Mi-Ock Lee: College of Pharmacy, Seoul National University, Seoul 08826, Korea
Gyu-Sang Hong: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea; Corresponding author
Kyungreem Han: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea; Corresponding author
Tae Song Kim: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Corresponding author
Uhtaek Oh: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea; Corresponding author

Journal volume & issue: Vol. 43, no. 6
p. 114334

Abstract

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Summary: 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.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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