6K7H

Cryo-EM structure of the human P4-type flippase ATP8A1-CDC50 (E1 state class2)

6K7H の概要

• エントリーDOI: 10.2210/pdb6k7h/pdb
• EMDBエントリー: 9932
• 分子名称: Phospholipid-transporting ATPase, 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, membrane 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: 172781.06

構造登録者

Hiraizumi, M.,Yamashita, K.,Nishizawa, T.,Nureki, O. (登録日: 2019-06-07, 公開日: 2019-08-28, 最終更新日: 2025-06-25)

主引用文献

Hiraizumi, M.,Yamashita, K.,Nishizawa, T.,Nureki, O.
Cryo-EM structures capture the transport cycle of the P4-ATPase flippase.
Science, 365:1149-1155, 2019

PubMed Abstract: In eukaryotic membranes, type IV P-type adenosine triphosphatases (P4-ATPases) mediate the translocation of phospholipids from the outer to the inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here, we report the cryo-electron microscopy structures of six distinct intermediates of the human ATP8A1-CDC50a heterocomplex at resolutions of 2.6 to 3.3 angstroms, elucidating the lipid translocation cycle of this P4-ATPase. ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second transmembrane helices, thereby allowing phosphatidylserine binding. The phospholipid head group passes through the hydrophilic cleft, while the acyl chain is exposed toward the lipid environment. These findings advance our understanding of the flippase mechanism and the disease-associated mutants of P4-ATPases.

PubMed: 31416931
DOI: 10.1126/science.aay3353

実験手法

ELECTRON MICROSCOPY (3.22 Å)