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-Structure paper
タイトル | Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 119, Issue 14, Page e2118656119, Year 2022 |
掲載日 | 2022年4月5日 |
著者 | Meng-Ting Cheng / Yu Chen / Zhi-Peng Chen / Xin Liu / Zhiyong Zhang / Yuxing Chen / Wen-Tao Hou / Cong-Zhao Zhou / |
PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:35349344 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.36 - 3.98 Å |
構造データ | EMDB-31969, PDB-7vgh: EMDB-31970, PDB-7vgi: EMDB-31971, PDB-7vgj: |
化合物 | ChemComp-NAG: ChemComp-MG: ChemComp-P5S: |
由来 |
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キーワード | LIPID TRANSPORT/TRANSLOCASE / auto-inhibited / phosphorylated / lipid flippase / LIPID TRANSPORT / LIPID TRANSPORT-TRANSLOCASE complex / TRANSLOCASE/LIPID TRANSPORT / TRANSLOCASE-LIPID TRANSPORT complex |