5dqq: Difference between revisions
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<StructureSection load='5dqq' size='340' side='right'caption='[[5dqq]], [[Resolution|resolution]] 2.87Å' scene=''> | <StructureSection load='5dqq' size='340' side='right'caption='[[5dqq]], [[Resolution|resolution]] 2.87Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5dqq]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5dqq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DQQ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=66R:TRANS-NED+19'>66R</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.872Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=66R:TRANS-NED+19'>66R</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dqq OCA], [https://pdbe.org/5dqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dqq RCSB], [https://www.ebi.ac.uk/pdbsum/5dqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dqq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/TPC1_ARATH TPC1_ARATH] Functions as a voltage-gated inward-rectifying Ca(2+) channel (VDCC) across the vacuole membrane. Is one of the essential components of the slow vacuolar (SV) channel. Acts as the major ROS-responsive Ca(2+) channel and is the possible target of Al-dependent inhibition. Involved in the regulation of germination and stomatal movement.<ref>PMID:15464979</ref> <ref>PMID:15772667</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Two-pore channels (TPCs) comprise a subfamily (TPC1-3) of eukaryotic voltage- and ligand-gated cation channels with two non-equivalent tandem pore-forming subunits that dimerize to form quasi-tetramers. Found in vacuolar or endolysosomal membranes, they regulate the conductance of sodium and calcium ions, intravesicular pH, trafficking and excitability. TPCs are activated by a decrease in transmembrane potential and an increase in cytosolic calcium concentrations, are inhibited by low luminal pH and calcium, and are regulated by phosphorylation. Here we report the crystal structure of TPC1 from Arabidopsis thaliana at 2.87 A resolution as a basis for understanding ion permeation, channel activation, the location of voltage-sensing domains and regulatory ion-binding sites. We determined sites of phosphorylation in the amino-terminal and carboxy-terminal domains that are positioned to allosterically modulate cytoplasmic Ca(2+) activation. One of the two voltage-sensing domains (VSD2) encodes voltage sensitivity and inhibition by luminal Ca(2+) and adopts a conformation distinct from the activated state observed in structures of other voltage-gated ion channels. The structure shows that potent pharmacophore trans-Ned-19 (ref. 17) acts allosterically by clamping the pore domains to VSD2. In animals, Ned-19 prevents infection by Ebola virus and other filoviruses, presumably by altering their fusion with the endolysosome and delivery of their contents into the cytoplasm. | |||
Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana.,Kintzer AF, Stroud RM Nature. 2016 Mar 10;531(7593):258-62. doi: 10.1038/nature17194. PMID:26961658<ref>PMID:26961658</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5dqq" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Arabidopsis thaliana]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kintzer | [[Category: Kintzer AF]] | ||
[[Category: Stroud | [[Category: Stroud RM]] | ||
Revision as of 00:55, 29 June 2023
Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thalianaStructure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana
Structural highlights
FunctionTPC1_ARATH Functions as a voltage-gated inward-rectifying Ca(2+) channel (VDCC) across the vacuole membrane. Is one of the essential components of the slow vacuolar (SV) channel. Acts as the major ROS-responsive Ca(2+) channel and is the possible target of Al-dependent inhibition. Involved in the regulation of germination and stomatal movement.[1] [2] Publication Abstract from PubMedTwo-pore channels (TPCs) comprise a subfamily (TPC1-3) of eukaryotic voltage- and ligand-gated cation channels with two non-equivalent tandem pore-forming subunits that dimerize to form quasi-tetramers. Found in vacuolar or endolysosomal membranes, they regulate the conductance of sodium and calcium ions, intravesicular pH, trafficking and excitability. TPCs are activated by a decrease in transmembrane potential and an increase in cytosolic calcium concentrations, are inhibited by low luminal pH and calcium, and are regulated by phosphorylation. Here we report the crystal structure of TPC1 from Arabidopsis thaliana at 2.87 A resolution as a basis for understanding ion permeation, channel activation, the location of voltage-sensing domains and regulatory ion-binding sites. We determined sites of phosphorylation in the amino-terminal and carboxy-terminal domains that are positioned to allosterically modulate cytoplasmic Ca(2+) activation. One of the two voltage-sensing domains (VSD2) encodes voltage sensitivity and inhibition by luminal Ca(2+) and adopts a conformation distinct from the activated state observed in structures of other voltage-gated ion channels. The structure shows that potent pharmacophore trans-Ned-19 (ref. 17) acts allosterically by clamping the pore domains to VSD2. In animals, Ned-19 prevents infection by Ebola virus and other filoviruses, presumably by altering their fusion with the endolysosome and delivery of their contents into the cytoplasm. Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana.,Kintzer AF, Stroud RM Nature. 2016 Mar 10;531(7593):258-62. doi: 10.1038/nature17194. PMID:26961658[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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