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-Structure paper
タイトル | Cryo-EM structures capture the transport cycle of the P4-ATPase flippase. |
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ジャーナル・号・ページ | Science, Vol. 365, Issue 6458, Page 1149-1155, Year 2019 |
掲載日 | 2019年9月13日 |
著者 | Masahiro Hiraizumi / Keitaro Yamashita / Tomohiro Nishizawa / Osamu Nureki / |
PubMed 要旨 | In eukaryotic membranes, type IV P-type adenosine triphosphatases (P4-ATPases) mediate the translocation of phospholipids from the outer to the inner leaflet and maintain lipid asymmetry, which is ...In eukaryotic membranes, type IV P-type adenosine triphosphatases (P4-ATPases) mediate the translocation of phospholipids from the outer to the inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here, we report the cryo-electron microscopy structures of six distinct intermediates of the human ATP8A1-CDC50a heterocomplex at resolutions of 2.6 to 3.3 angstroms, elucidating the lipid translocation cycle of this P4-ATPase. ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second transmembrane helices, thereby allowing phosphatidylserine binding. The phospholipid head group passes through the hydrophilic cleft, while the acyl chain is exposed toward the lipid environment. These findings advance our understanding of the flippase mechanism and the disease-associated mutants of P4-ATPases. |
リンク | Science / PubMed:31416931 |
手法 | EM (単粒子) |
解像度 | 2.63 - 3.42 Å |
構造データ | EMDB-9931, PDB-6k7g: EMDB-9932, PDB-6k7h: EMDB-9933: EMDB-9934, PDB-6k7i: EMDB-9935, PDB-6k7j: EMDB-9936: EMDB-9937, PDB-6k7k: EMDB-9938: EMDB-9939, PDB-6k7l: EMDB-9940: |
化合物 | ChemComp-NAG: ChemComp-Y01: ChemComp-ACP: ChemComp-MG: ChemComp-ADP: ChemComp-ALF: ChemComp-BEF: ChemComp-D39: |
由来 |
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キーワード | MEMBRANE PROTEIN / flippase |