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- EMDB-31971: Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50A in ... -
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Open data
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Basic information
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Title | Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50A in the auto-inhibited E2Pi-PS state | |||||||||
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Function / homology | ![]() vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / protein localization to endosome / inner ear receptor cell development ...vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / protein localization to endosome / inner ear receptor cell development / phospholipid-translocating ATPase complex / ATPase-coupled intramembrane lipid transporter activity / phosphatidylserine floppase activity / positive regulation of protein exit from endoplasmic reticulum / xenobiotic transmembrane transport / phosphatidylcholine floppase activity / stereocilium / apical protein localization / bile acid metabolic process / P-type phospholipid transporter / bile acid and bile salt transport / cardiolipin binding / phospholipid translocation / transport vesicle membrane / azurophil granule membrane / Golgi organization / Ion transport by P-type ATPases / specific granule membrane / monoatomic ion transmembrane transport / regulation of chloride transport / sensory perception of sound / trans-Golgi network / positive regulation of neuron projection development / early endosome membrane / late endosome membrane / nuclear body / apical plasma membrane / negative regulation of DNA-templated transcription / Neutrophil degranulation / structural molecule activity / magnesium ion binding / Golgi apparatus / endoplasmic reticulum / ATP hydrolysis activity / nucleoplasm / ATP binding / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.98 Å | |||||||||
![]() | Chen MT / Chen Y / Chen ZP / Zhou CZ / Hou WT | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding. Authors: Meng-Ting Cheng / Yu Chen / Zhi-Peng Chen / Xin Liu / Zhiyong Zhang / Yuxing Chen / Wen-Tao Hou / Cong-Zhao Zhou / ![]() Abstract: SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell ...SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell membrane and eventually, cell death. Thus, defects in ATP8B1 are usually associated with severe human diseases, such as intrahepatic cholestasis. The present structures of ATP8B1 complexed with its auxiliary noncatalytic partners CDC50A and CDC50B reveal an autoinhibited state of ATP8B1 that could be released upon substrate binding. Moreover, release of this autoinhibition could be facilitated by the bile acids, which are key factors that alter the membrane asymmetry of hepatocytes. This enabled us to figure out a feedback loop of bile acids and lipids across the cell membrane. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 49.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.8 KB 12.8 KB | Display Display | ![]() |
Images | ![]() | 142.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 475.5 KB | Display | ![]() |
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Full document | ![]() | 475 KB | Display | |
Data in XML | ![]() | 5.8 KB | Display | |
Data in CIF | ![]() | 6.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vgjMC ![]() 7vghC ![]() 7vgiC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.013 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : ATP8B1-CDC50A complex
Entire | Name: ATP8B1-CDC50A complex |
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Components |
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-Supramolecule #1: ATP8B1-CDC50A complex
Supramolecule | Name: ATP8B1-CDC50A complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Phospholipid-transporting ATPase IC
Macromolecule | Name: Phospholipid-transporting ATPase IC / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: P-type phospholipid transporter |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 148.458562 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMSTERDS ETTFDEDSQP NDEVVPYSDD ETEDELDDQG SAVEPEQNR VNREAEENRE PFRKECTWQV KANDRKYHEQ PHFMNTKFLC IKESKYANNA IKTYKYNAFT FIPMNLFEQF K RAANLYFL ...String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMSTERDS ETTFDEDSQP NDEVVPYSDD ETEDELDDQG SAVEPEQNR VNREAEENRE PFRKECTWQV KANDRKYHEQ PHFMNTKFLC IKESKYANNA IKTYKYNAFT FIPMNLFEQF K RAANLYFL ALLILQAVPQ ISTLAWYTTL VPLLVVLGVT AIKDLVDDVA RHKMDKEINN RTCEVIKDGR FKVAKWKEIQ VG DVIRLKK NDFVPADILL LSSSEPNSLC YVETAELDGE TNLKFKMSLE ITDQYLQRED TLATFDGFIE CEEPNNRLDK FTG TLFWRN TSFPLDADKI LLRGCVIRNT DFCHGLVIFA GADTKIMKNS GKTRFKRTKI DYLMNYMVYT IFVVLILLSA GLAI GHAYW EAQVGNSSWY LYDGEDDTPS YRGFLIFWGY IIVLNTMVPI SLYVSVEVIR LGQSHFINWD LQMYYAEKDT PAKAR TTTL NEQLGQIHYI FSDKTGTLTQ NIMTFKKCCI NGQIYGDHRD ASQHNHNKIE QVDFSWNTYA DGKLAFYDHY LIEQIQ SGK EPEVRQFFFL LAVCHTVMVD RTDGQLNYQA ASPDEGALVN AARNFGFAFL ARTQNTITIS ELGTERTYNV LAILDFN SD RKRMSIIVRT PEGNIKLYCK GADTVIYERL HRMNPTKQET QDALDIFANE TLRTLCLCYK EIEEKEFTEW NKKFMAAS V ASTNRDEALD KVYEEIEKDL ILLGATAIED KLQDGVPETI SKLAKADIKI WVLTGDKKET AENIGFACEL LTEDTTICY GEDINSLLHA RMENQRNRGG VYAKFAPPVQ ESFFPPGGNR ALIITGSWLN EILLEKKTKR NKILKLKFPR TEEERRMRTQ SKRRLEAKK EQRQKNFVDL ACECSAVICC RVTPKQKAMV VDLVKRYKKA ITLAIGDGAN DVNMIKTAHI GVGISGQEGM Q AVMSSDYS FAQFRYLQRL LLVHGRWSYI RMCKFLRYFF YKNFAFTLVH FWYSFFNGYS AQTAYEDWFI TLYNVLYTSL PV LLMGLLD QDVSDKLSLR FPGLYIVGQR DLLFNYKRFF VSLLHGVLTS MILFFIPLGA YLQTVGQDGE APSDYQSFAV TIA SALVIT VNFQIGLDTS YWTFVNAFSI FGSIALYFGI MFDFHSAGIH VLFPSAFQFT GTASNALRQP YIWLTIILAV AVCL LPVVA IRFLSMTIWP SESDKIQKHR KRLKAEEQWQ RRQQVFRRGV STRRSAYAFS HQRGYADLIS SGRSIRKKRS PLDAI VADG TAEYRRTGDS |
-Macromolecule #2: Cell cycle control protein 50A
Macromolecule | Name: Cell cycle control protein 50A / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.845746 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASMAMNYNA KDEVDGGPPC APGGTAKTRR PDNTAFKQQR LPAWQPILTA GTVLPIFFII GLIFIPIGIG IFVTSNNIRE IEIDYTGTE PSSPCNKCLS PDVTPCFCTI NFTLEKSFEG NVFMYYGLSN FYQNHRRYVK SRDDSQLNGD SSALLNPSKE C EPYRRNED ...String: MASMAMNYNA KDEVDGGPPC APGGTAKTRR PDNTAFKQQR LPAWQPILTA GTVLPIFFII GLIFIPIGIG IFVTSNNIRE IEIDYTGTE PSSPCNKCLS PDVTPCFCTI NFTLEKSFEG NVFMYYGLSN FYQNHRRYVK SRDDSQLNGD SSALLNPSKE C EPYRRNED KPIAPCGAIA NSMFNDTLEL FLIGNDSYPI PIALKKKGIA WWTDKNVKFR NPPGGDNLEE RFKGTTKPVN WL KPVYMLD SDPDNNGFIN EDFIVWMRTA ALPTFRKLYR LIERKSDLHP TLPAGRYSLN VTYNYPVHYF DGRKRMILST ISW MGGKNP FLGIAYIAVG SISFLLGVVL LVINHKYRNS SNTADITIHH HHHH |
-Macromolecule #3: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
Macromolecule | Name: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine type: ligand / ID: 3 / Number of copies: 1 / Formula: P5S |
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Molecular weight | Theoretical: 792.075 Da |
Chemical component information | ![]() ChemComp-P5S: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: LAB6 |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.98 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Number images used: 160435 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |