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-Structure paper
タイトル | Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 4142, Year 2019 |
掲載日 | 2019年9月12日 |
![]() | Lin Bai / Amanda Kovach / Qinglong You / Hao-Chi Hsu / Gongpu Zhao / Huilin Li / ![]() |
PubMed 要旨 | The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry. The enzyme complex exists in an autoinhibited form in the absence of an activator and is ...The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry. The enzyme complex exists in an autoinhibited form in the absence of an activator and is specifically activated by phosphatidylinositol-4-phosphate (PI4P), although the underlying mechanisms have been unclear. Here we report the cryo-EM structures of intact Drs2p-Cdc50p isolated from S. cerevisiae in apo form and in the PI4P-activated form at 2.8 Å and 3.3 Å resolution, respectively. The structures reveal that the Drs2p C-terminus lines a long groove in the cytosolic regulatory region to inhibit the flippase activity. PIP4 binding in a cytosol-proximal membrane region triggers a 90° rotation of a cytosolic helix switch that is located just upstream of the inhibitory C-terminal peptide. The rotation of the helix switch dislodges the C-terminus from the regulatory region, activating the flippase. |
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手法 | EM (単粒子) |
解像度 | 2.8 - 3.3 Å |
構造データ | EMDB-20467, PDB-6psx: EMDB-20468, PDB-6psy: |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | TRANSLOCASE / complex / phospholipid flippase / P-type ATPase |