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 language | English (US) |
|---|---|
| Pages (from-to) | 196-201 |
| Number of pages | 6 |
| Journal | Nature |
| Volume | 531 |
| Issue number | 7593 |
| DOIs | |
| State | Published - Mar 10 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana
AU - Guo, Jiangtao
AU - Zeng, Weizhong
AU - Chen, Qingfeng
AU - Lee, Changkeun
AU - Chen, Liping
AU - Yang, Yi
AU - Cang, Chunlei
AU - Ren, Dejian
AU - Jiang, Youxing
PY - 2016/3/10
Y1 - 2016/3/10
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84960906119&partnerID=8YFLogxK
U2 - 10.1038/nature16446
DO - 10.1038/nature16446
M3 - Article
C2 - 26689363
AN - SCOPUS:84960906119
VL - 531
SP - 196
EP - 201
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7593
ER -