|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6lkn' size='340' side='right'caption='[[6lkn]], [[Resolution|resolution]] 3.90Å' scene=''> | | <StructureSection load='6lkn' size='340' side='right'caption='[[6lkn]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lkn]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LKN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LKN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lkn]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LKN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AH2:1-deoxy-alpha-D-mannopyranose'>AH2</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.9Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AH2:1-deoxy-alpha-D-mannopyranose'>AH2</scene>, <scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATP11C, ATPIG, ATPIQ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TMEM30A, C6orf67, CDC50A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lkn OCA], [https://pdbe.org/6lkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lkn RCSB], [https://www.ebi.ac.uk/pdbsum/6lkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lkn ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/P-type_phospholipid_transporter P-type phospholipid transporter], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.6.2.1 7.6.2.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lkn OCA], [http://pdbe.org/6lkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lkn RCSB], [http://www.ebi.ac.uk/pdbsum/6lkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lkn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AT11C_HUMAN AT11C_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/AT11C_HUMAN AT11C_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AT11C_HUMAN AT11C_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]<ref>PMID:26944472</ref> [[http://www.uniprot.org/uniprot/CC50A_HUMAN CC50A_HUMAN]] Accessory 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. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediate the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations.<ref>PMID:20510206</ref> <ref>PMID:20947505</ref> <ref>PMID:20961850</ref> <ref>PMID:21289302</ref> | + | [https://www.uniprot.org/uniprot/AT11C_HUMAN AT11C_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]<ref>PMID:26944472</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 30: |
Line 28: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: P-type phospholipid transporter]]
| + | [[Category: Abe K]] |
| - | [[Category: Abe, K]] | + | [[Category: Hasegawa K]] |
| - | [[Category: Hasegawa, K]] | + | [[Category: Irie K]] |
| - | [[Category: Irie, K]] | + | [[Category: Nakanishi H]] |
| - | [[Category: Nakanishi, H]] | + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Flippase]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: P-type atpase]]
| + | |
| - | [[Category: Phosphatidylserine]]
| + | |
| Structural highlights
6lkn is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
AT11C_HUMAN The disease is caused by mutations affecting the gene represented in this entry.
Function
AT11C_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 PubMed
ATP11C, a member of the P4-ATPase flippase, translocates phosphatidylserine from the outer to the inner plasma membrane leaflet, and maintains the asymmetric distribution of phosphatidylserine in the living cell. We present the crystal structures of a human plasma membrane flippase, ATP11C-CDC50A complex, in a stabilized E2P conformation. The structure revealed a deep longitudinal crevice along transmembrane helices continuing from the cell surface to the phospholipid occlusion site in the middle of the membrane. We observed that the extension of the crevice on the exoplasmic side is open, and the complex is therefore in an outward-open E2P state, similar to a recently reported cryo-EM structure of yeast flippase Drs2p-Cdc50p complex. We noted extra densities, most likely bound phosphatidylserines, in the crevice and in its extension to the extracellular side. One was close to the phosphatidylserine occlusion site as previously reported for the human ATP8A1-CDC50A complex, and the other in a cavity at the surface of the exoplasmic leaflet of the bilayer. Substitutions in either of the binding sites or along the path between them impaired specific ATPase and transport activities. These results provide evidence that the observed crevice is the conduit along which phosphatidylserine traverses from the outer leaflet to its occlusion site in the membrane and suggest that the exoplasmic cavity is important for phospholipid recognition. They also yield insights into how phosphatidylserine is incorporated from the outer leaflet of the plasma membrane into the transmembrane.
Crystal structure of a human plasma membrane phospholipid flippase.,Nakanishi H, Irie K, Segawa K, Hasegawa K, Fujiyoshi Y, Nagata S, Abe K J Biol Chem. 2020 Jun 3. pii: RA120.014144. doi: 10.1074/jbc.RA120.014144. PMID:32493773[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Arashiki N, Takakuwa Y, Mohandas N, Hale J, Yoshida K, Ogura H, Utsugisawa T, Ohga S, Miyano S, Ogawa S, Kojima S, Kanno H. ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia. Haematologica. 2016 May;101(5):559-65. doi: 10.3324/haematol.2016.142273. Epub, 2016 Mar 4. PMID:26944472 doi:http://dx.doi.org/10.3324/haematol.2016.142273
- ↑ Nakanishi H, Irie K, Segawa K, Hasegawa K, Fujiyoshi Y, Nagata S, Abe K. Crystal structure of a human plasma membrane phospholipid flippase. J Biol Chem. 2020 Jun 3. pii: RA120.014144. doi: 10.1074/jbc.RA120.014144. PMID:32493773 doi:http://dx.doi.org/10.1074/jbc.RA120.014144
|
