Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana

Jiangtao Guo, Weizhong Zeng, Qingfeng Chen, Changkeun Lee, Liping Chen, Yi Yang, Chunlei Cang, Dejian Ren, Youxing Jiang

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Abstract

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 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 from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain, the conformational changes of which are coupled to the pair of inner helices from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing the second voltage-sensing domain in the resting state and shift 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.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalNature
Volume531
Issue number7593
DOIs
StatePublished - Mar 10 2016

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    Guo, J., Zeng, W., Chen, Q., Lee, C., Chen, L., Yang, Y., Cang, C., Ren, D., & Jiang, Y. (2016). Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. Nature, 531(7593), 196-201. https://doi.org/10.1038/nature16446