| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 6, Pp 114334- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114334 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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