Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for activation of voltage sensor domains in an ion channel TPC1.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 115, Issue 39, Page E9095-E9104, Year 2018
Publish date	Sep 25, 2018
Authors	Alexander F Kintzer / Evan M Green / Pawel K Dominik / Michael Bridges / Jean-Paul Armache / Dawid Deneka / Sangwoo S Kim / Wayne Hubbell / Anthony A Kossiakoff / Yifan Cheng / Robert M Stroud /
PubMed Abstract	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 ...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-binding site (Ca), 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 to a cytoplasmic site (Ca). An X-ray structure with Ca removed and a near-atomic resolution cryo-EM structure with Ca 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 ions for activation.
External links	Proc Natl Acad Sci U S A / PubMed:30190435 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	3.3 - 3.7 Å
Structure data	8956 6e1k EMDB-8956, PDB-6e1k: Structure of AtTPC1(DDE) reconstituted in saposin A with cat06 Fab Method: EM (single particle) / Resolution: 3.3 Å 8957 6e1m EMDB-8957, PDB-6e1m: Structure of AtTPC1(DDE) reconstituted in saposin A Method: EM (single particle) / Resolution: 3.3 Å 8958 6e1n EMDB-8958, PDB-6e1n: Structure of AtTPC1(DDE) in state 1 Method: EM (single particle) / Resolution: 3.7 Å 8960 6e1p EMDB-8960, PDB-6e1p: Structure of AtTPC1(DDE) in state 2 Method: EM (single particle) / Resolution: 3.7 Å PDB-6cx0: Structure of AtTPC1 D376A Method: X-RAY DIFFRACTION / Resolution: 3.501 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-FJ7: (1S,3R)-1-(3-{[4-(2-fluorophenyl)piperazin-1-yl]methyl}-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ChemComp-PLM: PALMITIC ACID ChemComp-HOH: WATER ChemComp-3PH: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE
Source	arabidopsis thaliana (thale cress) homo sapiens (human)
Keywords	membrane protein/inhibitor / Ion channel / Two-pore channel / TPC1 / resting-state / closed / inactive / MEMBRANE PROTEIN / membrane protein-inhibitor complex