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Yorodumi- EMDB-31969: Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50B in ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31969 | |||||||||
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Title | Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50B in the auto-inhibited E2P state | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / inner ear receptor cell development / phospholipid-translocating ATPase complex / ATPase-coupled intramembrane lipid transporter activity ...vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / 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 / Golgi organization / Ion transport by P-type ATPases / monoatomic ion transmembrane transport / regulation of chloride transport / sensory perception of sound / trans-Golgi network / membrane => GO:0016020 / nuclear body / apical plasma membrane / negative regulation of DNA-templated transcription / Golgi apparatus / magnesium ion binding / endoplasmic reticulum / ATP hydrolysis activity / nucleoplasm / ATP binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.39 Å | |||||||||
Authors | Chen MT / Chen Y | |||||||||
Funding support | China, 2 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 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 | emd_31969.map.gz | 49.3 MB | EMDB map data format | |
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Header (meta data) | emd-31969-v30.xml emd-31969.xml | 12.8 KB 12.8 KB | Display Display | EMDB header |
Images | emd_31969.png | 142.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31969 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31969 | HTTPS FTP |
-Related structure data
Related structure data | 7vghMC 7vgiC 7vgjC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31969.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.074 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : ATP8B1-CDC50B complex
Entire | Name: ATP8B1-CDC50B complex |
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Components |
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-Supramolecule #1: ATP8B1-CDC50B complex
Supramolecule | Name: ATP8B1-CDC50B complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Cell cycle control protein 50B
Macromolecule | Name: Cell cycle control protein 50B / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.307391 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSHHHHHHGS GSMTWSATAR GAHQPDNTAF TQQRLPAWQP LLSASIALPL FFCAGLAFIG LGLGLYYSSN GIKELEYDYT GDPGTGNCS VCAAAGQGRA LPPPCSCAWY FSLPELFQGP VYLYYELTNF YQNNRRYGVS RDDAQLSGLP SALRHPVNEC A PYQRSAAG ...String: MSHHHHHHGS GSMTWSATAR GAHQPDNTAF TQQRLPAWQP LLSASIALPL FFCAGLAFIG LGLGLYYSSN GIKELEYDYT GDPGTGNCS VCAAAGQGRA LPPPCSCAWY FSLPELFQGP VYLYYELTNF YQNNRRYGVS RDDAQLSGLP SALRHPVNEC A PYQRSAAG LPIAPCGAIA NSLFNDSFSL WHQRQPGGPY VEVPLDRSGI AWWTDYHVKF RNPPLVNGSL ALAFQGTAPP PN WRRPVYE LSPDPNNTGF INQDFVVWMR TAALPTFRKL YARIRQGNYS AGLPRGAYRV NITYNYPVRA FGGHKLLIFS SIS WMGGKN PFLGIAYLVV GSLCILTGFV MLVVYIRYQD QDDDDEE |
-Macromolecule #2: Phospholipid-transporting ATPase IC
Macromolecule | Name: Phospholipid-transporting ATPase IC / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: P-type phospholipid transporter |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 148.538547 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 FS(PHD)KTGTLTQ NIMTFKKCCI NGQIYGDHRD ASQHNHNKIE QVDFSWNTYA DGKLAFYDHY LI EQIQSGK EPEVRQFFFL LAVCHTVMVD RTDGQLNYQA ASPDEGALVN AARNFGFAFL ARTQNTITIS ELGTERTYNV LAI LDFNSD RKRMSIIVRT PEGNIKLYCK GADTVIYERL HRMNPTKQET QDALDIFANE TLRTLCLCYK EIEEKEFTEW NKKF MAASV ASTNRDEALD KVYEEIEKDL ILLGATAIED KLQDGVPETI SKLAKADIKI WVLTGDKKET AENIGFACEL LTEDT TICY GEDINSLLHA RMENQRNRGG VYAKFAPPVQ ESFFPPGGNR ALIITGSWLN EILLEKKTKR NKILKLKFPR TEEERR MRT QSKRRLEAKK EQRQKNFVDL ACECSAVICC RVTPKQKAMV VDLVKRYKKA ITLAIGDGAN DVNMIKTAHI GVGISGQ EG MQAVMSSDYS FAQFRYLQRL LLVHGRWSYI RMCKFLRYFF YKNFAFTLVH FWYSFFNGYS AQTAYEDWFI TLYNVLYT S LPVLLMGLLD QDVSDKLSLR FPGLYIVGQR DLLFNYKRFF VSLLHGVLTS MILFFIPLGA YLQTVGQDGE APSDYQSFA VTIASALVIT VNFQIGLDTS YWTFVNAFSI FGSIALYFGI MFDFHSAGIH VLFPSAFQFT GTASNALRQP YIWLTIILAV AVCLLPVVA IRFLSMTIWP SESDKIQKHR KRLKAEEQWQ RRQQVFRRGV STRRSAYAFS HQRGYADLIS SGRSIRKKRS P LDAIVADG TAEYRRTGDS |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #7: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 7 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 160435 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |