EMD-31969
Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50B in the auto-inhibited E2P state
EMD-31969
Single-particle3.39 Å
Deposition: 16/09/2021Map released: 30/03/2022
Last modified: 12/10/2022
Sample Organism:
Homo sapiens
Sample: ATP8B1-CDC50B complex
Fitted models: 7vgh (Avg. Q-score: 0.522)
Deposition Authors: Chen MT
,
Chen Y
Sample: ATP8B1-CDC50B complex
Fitted models: 7vgh (Avg. Q-score: 0.522)
Deposition Authors: Chen MT
,
Chen Y
Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding.
Cheng MT ,
Chen Y ,
Chen ZP ,
Liu X ,
Zhang Z ,
Chen Y ,
Hou WT ,
Zhou CZ
(2022) PNAS , 119 , e2118656119 - e2118656119
,
Chen Y ,
Chen ZP ,
Liu X ,
Zhang Z ,
Chen Y ,
Hou WT ,
Zhou CZ
(2022) PNAS , 119 , e2118656119 - e2118656119
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.
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.