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

Article

关键词: OF-FUNCTION ALLELE;    SHAKER K+ CHANNEL;    GATING-CHARGE;    CRYSTAL-STRUCTURE;    ION CHANNELS;    WILD-TYPE;    CALCIUM;    SODIUM;    NAADP;    PERSPECTIVE;   

DOI  :  10.1038/nature16446

来源: SCIE

【 摘 要 】

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 Ba-2-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.

【 授权许可】

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