+
検索条件

キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

-
Structure paper

タイトル	Structural basis for activation of voltage sensor domains in an ion channel TPC1.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 115, Issue 39, Page E9095-E9104, Year 2018
掲載日	2018年9月25日
著者	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 要旨	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.
リンク	Proc Natl Acad Sci U S A / PubMed:30190435 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.3 - 3.7 Å
構造データ	8956 6e1k EMDB-8956, PDB-6e1k: Structure of AtTPC1(DDE) reconstituted in saposin A with cat06 Fab 手法: EM (単粒子) / 解像度: 3.3 Å 8957 6e1m EMDB-8957, PDB-6e1m: Structure of AtTPC1(DDE) reconstituted in saposin A 手法: EM (単粒子) / 解像度: 3.3 Å 8958 6e1n EMDB-8958, PDB-6e1n: Structure of AtTPC1(DDE) in state 1 手法: EM (単粒子) / 解像度: 3.7 Å 8960 6e1p EMDB-8960, PDB-6e1p: Structure of AtTPC1(DDE) in state 2 手法: EM (単粒子) / 解像度: 3.7 Å PDB-6cx0: Structure of AtTPC1 D376A 手法: X-RAY DIFFRACTION / 解像度: 3.501 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン 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 / パルミチン酸 / パルミチン酸 ChemComp-HOH: WATER / 水 ChemComp-3PH: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE / ジステアロイルホスファチジン酸 / ホスファチジン酸
由来	arabidopsis thaliana (シロイヌナズナ) homo sapiens (ヒト)
キーワード	membrane protein/inhibitor (生体膜) / Ion channel (イオンチャネル) / Two-pore channel / TPC1 / resting-state / closed / inactive / MEMBRANE PROTEIN (膜タンパク質) / membrane protein-inhibitor complex (生体膜)