7VSG

Cryo-EM structure of a human ATP11C-CDC50A flippase reconstituted in the Nanodisc in PtdSer-occluded E2-Pi state.

7VSG の概要

• エントリーDOI: 10.2210/pdb7vsg/pdb
• EMDBエントリー: 32110
• 分子名称: Phospholipid-transporting ATPase IG, Cell cycle control protein 50A, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: flippase, p4-atpase, membrane protein, phospholipid transporter, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 167013.14

構造登録者

Nakanishii, H.,Abe, K. (登録日: 2021-10-26, 公開日: 2021-12-29, 最終更新日: 2024-11-13)

主引用文献

Nakanishi, H.,Hayashida, K.,Nishizawa, T.,Oshima, A.,Abe, K.
Cryo-EM of the ATP11C flippase reconstituted in Nanodiscs shows a distended phospholipid bilayer inner membrane around transmembrane helix 2.
J.Biol.Chem., 298:101498-101498, 2022

PubMed Abstract: ATP11C is a member of the P4-ATPase flippase family that mediates translocation of phosphatidylserine (PtdSer) across the lipid bilayer. In order to characterize the structure and function of ATP11C in a model natural lipid environment, we revisited and optimized a quick procedure for reconstituting ATP11C into Nanodiscs using methyl-β-cyclodextrin as a reagent for the detergent removal. ATP11C was efficiently reconstituted with the endogenous lipid, or the mixture of endogenous lipid and synthetic dioleoylphosphatidylcholine (DOPC)/dioleoylphosphatidylserine (DOPS), all of which retained the ATPase activity. We obtained 3.4 Å and 3.9 Å structures using single-particle cryo-electron microscopy (cryo-EM) of AlF- and BeF-stabilized ATP11C transport intermediates, respectively, in a bilayer containing DOPS. We show that the latter exhibited a distended inner membrane around ATP11C transmembrane helix 2, possibly reflecting the perturbation needed for phospholipid release to the lipid bilayer. Our structures of ATP11C in the lipid membrane indicate that the membrane boundary varies upon conformational changes of the enzyme and is no longer flat around the protein, a change that likely contributes to phospholipid translocation across the membrane leaflets.

PubMed: 34922944
DOI: 10.1016/j.jbc.2021.101498

実験手法

ELECTRON MICROSCOPY (3.9 Å)