Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.
Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.
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DOI：
10.1038/nature16446
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发表时间：
2016-03-10
期刊：
影响因子：
64.8
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Guo J;Zeng W;Chen Q;Lee C;Chen L;Yang Y;Cang C;Ren D;Jiang Y
两孔通道(TPC)在每个亚基中含有两个拷贝的Shaker样六跨膜结构域(6-TM)，以细胞器阳离子通道的形式在动物和植物中广泛表达。在这里，我们提出了拟南芥液泡两孔通道的第一个晶体结构，AtTPC1，它的功能是同源二聚体。AtTPC1的激活需要电压和胞内钙离子的共同作用。Ca~(2+)与胞质EF-Hand结构域的结合触发与来自第一个6-TM结构域的一对孔衬内螺旋(IS6螺旋)耦合的构象变化，而膜电位仅激活第二个电压敏感结构域(VSD2)，其构象变化与来自第二个6-TM结构域的一对内螺旋(IIS6螺旋)耦合。鲁米那钙离子或Ba2+可通过稳定静息状态下的VSD2来调制电压激活，并使电压激活向更正的电位移动。我们的Ba2+绑定AtTPC1结构揭示了处于静止状态的电压传感器，提供了迄今未见的对电压门控通道中的一般电压门控机制的结构洞察。
Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here, we present the first crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices (IS6 helices) from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain (VSD2) whose conformational changes are coupled to the pair of inner helices (IIS6 helices) from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing VSD2 in the resting state and shifts voltage activation towards more positive potentials. Our Ba2+ bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels.