Pak, Sung min Ryu, Hyunil Lim, Sujin Nguyen, Thien Luan Yang, Sung wook Sumin, Kang Yu, Yeon Gyu Woo, Junhyuk Kim, Chanjin Cristina Fenollar-Ferrer John N. Wood, Mi-Ock Lee Hong, Gyu-Sang Han, Kyung reem Kim, Tae Song Oh, Uh taek 2024-06-11T02:30:21Z 2024-06-11T02:30:21Z 2024-06-10 2024-06 2211-1247 https://pubs.kist.re.kr/handle/201004/150044 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. English Cell Press Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel Article 10.1016/j.celrep.2024.114334 1 Cell Reports, v.43, no.6 Cell Reports 43 6 Y scie scopus 001257338400001 Cell Biology Cell Biology Article AMINO-ACIDS MECHANISMS PIEZO1 MECHANOTRANSDUCTION CURRENTS RINGS MSCL ACTIVATED ION-CHANNEL PROTEIN STRUCTURES