6E1M

Structure of AtTPC1(DDE) reconstituted in saposin A

6E1M の概要

• エントリーDOI: 10.2210/pdb6e1m/pdb
• 関連するPDBエントリー: 6E1K
• EMDBエントリー: 8956 8957 8958 8960
• 分子名称: Two pore calcium channel protein 1, CALCIUM ION, PALMITIC ACID, ... (5 entities in total)
• 機能のキーワード: two-pore channel, membrane protein
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 174374.88

構造登録者

Kintzer, A.F.,Green, E.M.,Cheng, Y.,Stroud, R.M. (登録日: 2018-07-10, 公開日: 2018-09-19, 最終更新日: 2024-12-25)

主引用文献

Kintzer, A.F.,Green, E.M.,Dominik, P.K.,Bridges, M.,Armache, J.P.,Deneka, D.,Kim, S.S.,Hubbell, W.,Kossiakoff, A.A.,Cheng, Y.,Stroud, R.M.
Structural basis for activation of voltage sensor domains in an ion channel TPC1.
Proc. Natl. Acad. Sci. U.S.A., 115:E9095-E9104, 2018

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 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.

PubMed: 30190435
DOI: 10.1073/pnas.1805651115

実験手法

ELECTRON MICROSCOPY (3.3 Å)