Crystal structures of the TRIC trimeric intracellular cation channel orthologues.
Crystal structures of the TRIC trimeric intracellular cation channel orthologues.
复制标题
TRIC 三聚体细胞内阳离子通道直系同源物的晶体结构。
作者：
肌浆网（SR）和内质网（ER）释放Ca2+对肌肉收缩、细胞生长、细胞凋亡、学习和记忆至关重要。三聚体胞内阳离子（TRIC）通道最近被确定为平衡SR和ER膜电位的阳离子通道，并与Ca2+信号传导和体内平衡有关。在此，我们展示了处于关闭状态的原核生物TRIC通道的晶体结构，以及对原核生物和真核生物TRIC通道基于结构的功能分析。每个三聚体亚基由7个跨膜（TM）螺旋组成，具有两个反向重复区域。电生理、生化和生物物理分析表明，TRIC通道在每个亚基内都有一个离子传导孔，并且三聚体的形成有助于蛋白质的稳定性。对称相关的TM2和TM5螺旋在保守的甘氨酸簇处弯折，这些弯折对通道活性很重要。此外，TM2和TM5螺旋的弯折在每个亚基界面处产生侧向窗孔。出乎意料的是，这些侧向窗孔被脂质分子占据。这项研究为该离子通道超家族的分子机制提供了结构和功能框架。
Ca2+ release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca2+ signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels. Each trimer subunit consists of seven transmembrane (TM) helices with two inverted repeated regions. The electrophysiological, biochemical and biophysical analyses revealed that TRIC channels possess an ion-conducting pore within each subunit, and that the trimer formation contributes to the stability of the protein. The symmetrically related TM2 and TM5 helices are kinked at the conserved glycine clusters, and these kinks are important for the channel activity. Furthermore, the kinks of the TM2 and TM5 helices generate lateral fenestrations at each subunit interface. Unexpectedly, these lateral fenestrations are occupied with lipid molecules. This study provides the structural and functional framework for the molecular mechanism of this ion channel superfamily.
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影响因子：
64.8
作者：
Fan G;Baker ML;Wang Z;Baker MR;Sinyagovskiy PA;Chiu W;Ludtke SJ;Serysheva II
通讯作者：
Serysheva II
影响因子：
4
作者：
Berridge, Michael J.
通讯作者：
Berridge, Michael J.
影响因子：
64.8
作者：
Hino, Tomoya;Arakawa, Takatoshi;Iwanari, Hiroko;Yurugi-Kobayashi, Takami;Ikeda-Suno, Chiyo;Nakada-Nakura, Yoshiko;Kusano-Arai, Osamu;Weyand, Simone;Shimamura, Tatsuro;Nomura, Norimichi;Cameron, Alexander D.;Kobayashi, Takuya;Hamakubo, Takao;Iwata, So;Murata, Takeshi
通讯作者：
Murata, Takeshi
影响因子：
4.8
作者：
Kuo, Mario Meng-Chiang;Saimi, Yoshiro;Choe, Senyon
通讯作者：
Choe, Senyon
影响因子：
56.9
作者：
Levene, MJ;Korlach, J;Webb, WW
通讯作者：
Webb, WW