Structure of Voltage gated Two pore Channel TPC1 from Arabidopsis thaliana
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.
Nature