@article{a075e61220194d70ad7a75fc0aef1cbe,
title = "Voltage-gating and cytosolic Ca2+ activation mechanisms of arabidopsis two-pore channel AtTPC1",
abstract = "Arabidopsis thaliana two-pore channel AtTPC1 is a voltage-gated, Ca2+-modulated, nonselective cation channel that is localized in the vacuolar membrane and responsible for generating slow vacuolar (SV) current. Under depolarizing membrane potential, cytosolic Ca2+ activates AtTPC1 by binding at the EF-hand domain, whereas luminal Ca2+ inhibits the channel by stabilizing the voltage-sensing domain II (VSDII) in the resting state. Here, we present 2.8 to 3.3 {\AA} cryoelectron microscopy (cryo-EM) structures of AtTPC1 in two conformations, one in closed conformation with unbound EF-hand domain and resting VSDII and the other in a partially open conformation with Ca2+-bound EF-hand domain and activated VSDII. Structural comparison between the two different conformations allows us to elucidate the structural mechanisms of voltage gating, cytosolic Ca2+ activation, and their coupling in AtTPC1. This study also provides structural insight into the general voltage-gating mechanism among voltage-gated ion channels.",
keywords = "Ca activation, Coupling, TPC, Voltage gating",
author = "Fan Ye and Lingyi Xu and Xiaoxiao Li and Weizhong Zeng and Ninghai Gan and Cheng Zhao and Wei Yang and Youxing Jiang and Jiangtao Guo",
note = "Funding Information: ACKNOWLEDGMENTS. Single-particle cryo-EM data were collected at the Center of Cryo-Electron Microscopy at Zhejiang University. We thank Dr. Xing Zhang and Dr. Shenghai Chang for support in facility access and data acquisition. This work was supported in part by the Ministry of Science and Technology (2020YFA0908501 and 2018YFA0508100 to J.G.), the National Natural Science Foundation of China (31870724 to J.G.; 82030108, 31872796, and 81571127 to W.Y.), National Major Special Project on New Drug Innovation of China (2018ZX09711001-004-005 to W.Y.), Zhejiang Provincial Natural Science Foundation (LR19C050002 to J.G.; LR16H090001 to W.Y.), and the Fundamental Research Funds for the Central Universities (2021FZZX001-28 to J.G.). J.G. is supported by Ministry of Education Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University. Y.J. is supported by the HHMI (Y.J.) and by grants from the NIH (R35GM140892 to Y.J.) and the Welch Foundation (Grant I-1578 to Y.J.). Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = dec,
day = "7",
doi = "10.1073/pnas.2113946118",
language = "English (US)",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "49",
}