Publication Date:
2015-12-23
Description:
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 Ca(2+). Ca(2+) 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 Ca(2+) or Ba(2+) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841471/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841471/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Jiangtao -- Zeng, Weizhong -- Chen, Qingfeng -- Lee, Changkeun -- Chen, Liping -- Yang, Yi -- Cang, Chunlei -- Ren, Dejian -- Jiang, Youxing -- GM079179/GM/NIGMS NIH HHS/ -- NS055293/NS/NINDS NIH HHS/ -- NS074257/NS/NINDS NIH HHS/ -- R01 GM079179/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 10;531(7593):196-201. doi: 10.1038/nature16446. Epub 2015 Dec 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA. ; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA. ; Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26689363" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Arabidopsis/*chemistry
;
Arabidopsis Proteins/*chemistry/genetics/metabolism
;
Barium/metabolism
;
Binding Sites
;
Calcium/metabolism/pharmacology
;
Calcium Channels/*chemistry/genetics/metabolism
;
Crystallography, X-Ray
;
Cytosol/metabolism
;
EF Hand Motifs
;
Electric Conductivity
;
HEK293 Cells
;
Humans
;
Ion Channel Gating/drug effects
;
Ion Transport/drug effects
;
Membrane Potentials/drug effects
;
Models, Molecular
;
Molecular Sequence Data
;
Protein Multimerization
;
Protein Structure, Quaternary
;
Protein Subunits/chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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