title: Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.
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 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.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Changkeun
authors.initials: C
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Cang
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dejian
authors.initials: D
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Youxing
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000737:chemistry*; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D020832:EF Hand Motifs; D004553:Electric Conductivity; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D000097903:Two-Pore Channels
chemical_list: D029681:Arabidopsis Proteins; D001464:Barium; D002118:Calcium; D015220:Calcium Channels; D021122:Protein Subunits; C498240:TPC1 protein, Arabidopsis; D000097903:Two-Pore Channels