7VGH

Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50B in the auto-inhibited E2P state

Summary for 7VGH

• Entry DOI: 10.2210/pdb7vgh/pdb
• EMDB information: 31969
• Descriptor: Cell cycle control protein 50B, Phospholipid-transporting ATPase IC, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: auto-inhibited, phosphorylated, lipid flippase, lipid transport, lipid transport-translocase complex, lipid transport/translocase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 191337.50

Authors

Chen, M.T.,Chen, Y. (deposition date: 2021-09-16, release date: 2022-03-30, Last modification date: 2022-10-12)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.39 Å)