6e1k: Difference between revisions
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==Structure of AtTPC1(DDE) reconstituted in saposin A with cat06 Fab== | |||
<StructureSection load='6e1k' size='340' side='right' caption='[[6e1k]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e1k]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E1K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E1K FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1k OCA], [http://pdbe.org/6e1k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e1k RCSB], [http://www.ebi.ac.uk/pdbsum/6e1k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1k ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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 == | |||
Voltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured an example of a resting-state VSD in an intact ion channel. To generate an activated-state VSD in the same channel we removed the luminal inhibitory Ca(2+)-binding site (Cai(2+)), which shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side but remains occluded on the luminal side and an intermediate activated state 2 in which the cytoplasmic solvent access to the gating charges closes, while luminal access partially opens. Activation can be thought of as moving a hydrophobic insulating region of the VSD from the external side to an alternate grouping on the internal side. This effectively moves the gating charges from the inside potential to that of the outside. Activation also requires binding of Ca(2+) to a cytoplasmic site (Caa(2+)). An X-ray structure with Caa(2+) removed and a near-atomic resolution cryo-EM structure with Cai(2+) removed define how dramatic conformational changes in the cytoplasmic domains may communicate with the VSD during activation. Together four structures provide a basis for understanding the voltage-dependent transition from resting to activated state, the tuning of VSD by thermodynamic stability, and this channel's requirement of cytoplasmic Ca(2+) ions for activation. | |||
Structural basis for activation of voltage sensor domains in an ion channel TPC1.,Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM Proc Natl Acad Sci U S A. 2018 Sep 6. pii: 1805651115. doi:, 10.1073/pnas.1805651115. PMID:30190435<ref>PMID:30190435</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6e1k" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cheng, Y]] | |||
[[Category: Green, E M]] | |||
[[Category: Kintzer, A F]] | |||
[[Category: Stroud, R M]] | |||
[[Category: Membrane protein]] | |||
[[Category: Two-pore channel]] | |||
Revision as of 22:51, 19 September 2018
Structure of AtTPC1(DDE) reconstituted in saposin A with cat06 FabStructure of AtTPC1(DDE) reconstituted in saposin A with cat06 Fab
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedVoltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured an example of a resting-state VSD in an intact ion channel. To generate an activated-state VSD in the same channel we removed the luminal inhibitory Ca(2+)-binding site (Cai(2+)), which shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side but remains occluded on the luminal side and an intermediate activated state 2 in which the cytoplasmic solvent access to the gating charges closes, while luminal access partially opens. Activation can be thought of as moving a hydrophobic insulating region of the VSD from the external side to an alternate grouping on the internal side. This effectively moves the gating charges from the inside potential to that of the outside. Activation also requires binding of Ca(2+) to a cytoplasmic site (Caa(2+)). An X-ray structure with Caa(2+) removed and a near-atomic resolution cryo-EM structure with Cai(2+) removed define how dramatic conformational changes in the cytoplasmic domains may communicate with the VSD during activation. Together four structures provide a basis for understanding the voltage-dependent transition from resting to activated state, the tuning of VSD by thermodynamic stability, and this channel's requirement of cytoplasmic Ca(2+) ions for activation. Structural basis for activation of voltage sensor domains in an ion channel TPC1.,Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM Proc Natl Acad Sci U S A. 2018 Sep 6. pii: 1805651115. doi:, 10.1073/pnas.1805651115. PMID:30190435[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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