7VGJ

Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50A in the auto-inhibited E2Pi-PS state

7VGJ の概要

• エントリーDOI: 10.2210/pdb7vgj/pdb
• EMDBエントリー: 31971
• 分子名称: Phospholipid-transporting ATPase IC, Cell cycle control protein 50A, O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (3 entities in total)
• 機能のキーワード: auto-inhibited, phosphorylated, lipid flippase, lipid transport, translocase-lipid transport complex, translocase/lipid transport
• 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: 191096.38

構造登録者

Chen, M.T.,Chen, Y.,Chen, Z.P.,Zhou, C.Z.,Hou, W.T.,Chen, Y. (登録日: 2021-09-16, 公開日: 2022-03-30, 最終更新日: 2024-10-16)

主引用文献

Cheng, M.T.,Chen, Y.,Chen, Z.P.,Liu, X.,Zhang, Z.,Chen, Y.,Hou, W.T.,Zhou, C.Z.
Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding.
Proc.Natl.Acad.Sci.USA, 119:e2118656119-e2118656119, 2022

PubMed Abstract: SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell membrane and eventually, cell death. Thus, defects in ATP8B1 are usually associated with severe human diseases, such as intrahepatic cholestasis. The present structures of ATP8B1 complexed with its auxiliary noncatalytic partners CDC50A and CDC50B reveal an autoinhibited state of ATP8B1 that could be released upon substrate binding. Moreover, release of this autoinhibition could be facilitated by the bile acids, which are key factors that alter the membrane asymmetry of hepatocytes. This enabled us to figure out a feedback loop of bile acids and lipids across the cell membrane.

PubMed: 35349344
DOI: 10.1073/pnas.2118656119

実験手法

ELECTRON MICROSCOPY (3.98 Å)