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-Structure paper
Title | Transport Cycle of Plasma Membrane Flippase ATP11C by Cryo-EM. |
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Journal, issue, pages | Cell Rep, Vol. 32, Issue 13, Page 108208, Year 2020 |
Publish date | Sep 29, 2020 |
Authors | Hanayo Nakanishi / Tomohiro Nishizawa / Katsumori Segawa / Osamu Nureki / Yoshinori Fujiyoshi / Shigekazu Nagata / Kazuhiro Abe / |
PubMed Abstract | ATP11C, a plasma membrane phospholipid flippase, maintains the asymmetric distribution of phosphatidylserine accumulated in the inner leaflet. Caspase-dependent inactivation of ATP11C is essential ...ATP11C, a plasma membrane phospholipid flippase, maintains the asymmetric distribution of phosphatidylserine accumulated in the inner leaflet. Caspase-dependent inactivation of ATP11C is essential for an apoptotic "eat me" signal, phosphatidylserine exposure, which prompts phagocytes to engulf cells. We show six cryo-EM structures of ATP11C at 3.0-4.0 Å resolution in five different states of the transport cycle. A structural comparison reveals phosphorylation-driven domain movements coupled with phospholipid binding. Three structures of phospholipid-bound states visualize phospholipid translocation accompanied by the rearrangement of transmembrane helices and an unwound portion at the occlusion site, and thus they detail the basis for head group recognition and the locality of the protein-bound acyl chains in transmembrane grooves. Invariant Lys880 and the surrounding hydrogen-bond network serve as a pivot point for helix bending and precise P domain inclination, which is crucial for dephosphorylation. The structures detail key features of phospholipid translocation by ATP11C, and a common basic mechanism for flippases is emerging. |
External links | Cell Rep / PubMed:32997992 |
Methods | EM (single particle) |
Resolution | 3.0 - 4.0 Å |
Structure data | EMDB-30163, PDB-7bsp: EMDB-30164, PDB-7bsq: EMDB-30165, PDB-7bss: EMDB-30167, PDB-7bsu: EMDB-30168, PDB-7bsv: EMDB-30169, PDB-7bsw: |
Chemicals | ChemComp-ACP: ChemComp-NAG: ChemComp-ALF: ChemComp-ADP: ChemComp-MG: ChemComp-MAN: ChemComp-P5S: ChemComp-AH2: ChemComp-HOH: ChemComp-PEE: |
Source |
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Keywords | MEMBRANE PROTEIN / Flippase / P-type ATPase / P4-ATPase / Phospholipid |