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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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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EF Hand Motifs
Arabidopsis
Membrane Potentials
Cations
Arabidopsis TPC1 protein

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Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. / Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Cang, Chunlei; Ren, Dejian; Jiang, Youxing.

In: Nature, Vol. 531, No. 7593, 10.03.2016, p. 196-201.

Research output: Contribution to journalArticle

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, vol. 531, no. 7593, pp. 196-201. https://doi.org/10.1038/nature16446
Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y et al. Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. Nature. 2016 Mar 10;531(7593):196-201. https://doi.org/10.1038/nature16446
Guo, Jiangtao ; Zeng, Weizhong ; Chen, Qingfeng ; Lee, Changkeun ; Chen, Liping ; Yang, Yi ; Cang, Chunlei ; Ren, Dejian ; Jiang, Youxing. / Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. In: Nature. 2016 ; Vol. 531, No. 7593. pp. 196-201.
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