7bsw | pdb_00007bsw
Cryo-EM structure of a human ATP11C-CDC50A flippase in PtdEtn-occluded E2-AlF state
Structural highlights
DiseaseAT11C_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionAT11C_HUMAN Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. In the cell membrane of erythrocytes, it is required to maintain phosphatidylserine (PS) in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for splenic macrophages (PubMed:26944472). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Required for B cell differentiation past the pro-B cell stage (By similarity). Seems to mediate PS flipping in pro-B cells (By similarity). May be involved in the transport of cholestatic bile acids (By similarity).[UniProtKB:Q9QZW0][1] Publication Abstract from PubMedATP11C, 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 A 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. Transport Cycle of Plasma Membrane Flippase ATP11C by Cryo-EM.,Nakanishi H, Nishizawa T, Segawa K, Nureki O, Fujiyoshi Y, Nagata S, Abe K Cell Rep. 2020 Sep 29;32(13):108208. doi: 10.1016/j.celrep.2020.108208. PMID:32997992[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
