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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24312 | ||||||||||||
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Title | The structure of human ABCG5/ABCG8 purified from yeast | ||||||||||||
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Function / homology | ![]() negative regulation of intestinal phytosterol absorption / negative regulation of intestinal cholesterol absorption / Defective ABCG8 causes GBD4 and sitosterolemia / Defective ABCG5 causes sitosterolemia / sterol transport / ABC transporters in lipid homeostasis / intestinal cholesterol absorption / phospholipid transport / cholesterol transfer activity / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate ...negative regulation of intestinal phytosterol absorption / negative regulation of intestinal cholesterol absorption / Defective ABCG8 causes GBD4 and sitosterolemia / Defective ABCG5 causes sitosterolemia / sterol transport / ABC transporters in lipid homeostasis / intestinal cholesterol absorption / phospholipid transport / cholesterol transfer activity / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / triglyceride homeostasis / bile acid signaling pathway / response to muscle activity / cholesterol efflux / response to ionizing radiation / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / response to nutrient / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / ATP-binding cassette (ABC) transporter complex / cholesterol homeostasis / transmembrane transport / receptor complex / apical plasma membrane / response to xenobiotic stimulus / protein heterodimerization activity / ATP hydrolysis activity / ATP binding / metal ion binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||||||||
![]() | Sun Y / Li X / Long T | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis of cholesterol efflux via ABCG subfamily transporters. Authors: Yingyuan Sun / Jin Wang / Tao Long / Xiaofeng Qi / Linda Donnelly / Nadia Elghobashi-Meinhardt / Leticia Esparza / Jonathan C Cohen / Xiao-Song Xie / Helen H Hobbs / Xiaochun Li / ![]() ![]() Abstract: The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular ...The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 8.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.9 KB 16.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.5 KB | Display | ![]() |
Images | ![]() | 103 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 366.8 KB | Display | ![]() |
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Full document | ![]() | 366.4 KB | Display | |
Data in XML | ![]() | 11.8 KB | Display | |
Data in CIF | ![]() | 15.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7r89MC ![]() 7r87C ![]() 7r88C ![]() 7r8aC ![]() 7r8bC ![]() 7r8cC ![]() 7r8dC ![]() 7r8eC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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: 0.832 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : ABCG1 transporter with ergosterol and Fab 2C7 bound
Entire | Name: ABCG1 transporter with ergosterol and Fab 2C7 bound |
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Components |
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-Supramolecule #1: ABCG1 transporter with ergosterol and Fab 2C7 bound
Supramolecule | Name: ABCG1 transporter with ergosterol and Fab 2C7 bound / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Molecular weight | Theoretical: 150 KDa |
-Supramolecule #2: ABCG1 transporter
Supramolecule | Name: ABCG1 transporter / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Fab 2C7
Supramolecule | Name: Fab 2C7 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: ATP-binding cassette sub-family G member 5
Macromolecule | Name: ATP-binding cassette sub-family G member 5 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO EC number: Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 74.437383 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGDLSSLTPG GSMGLQVNRG SQSSLEGAPA TAPEPHSLGI LHASYSVSHR VRPWWDITSC RQQWTRQILK DVSLYVESGQ IMCILGSSG SGKTTLLDAM SGRLGRAGTF LGEVYVNGRA LRREQFQDCF SYVLQSDTLL SSLTVRETLH YTALLAIRRG N PGSFQKKV ...String: MGDLSSLTPG GSMGLQVNRG SQSSLEGAPA TAPEPHSLGI LHASYSVSHR VRPWWDITSC RQQWTRQILK DVSLYVESGQ IMCILGSSG SGKTTLLDAM SGRLGRAGTF LGEVYVNGRA LRREQFQDCF SYVLQSDTLL SSLTVRETLH YTALLAIRRG N PGSFQKKV EAVMAELSLS HVADRLIGNY SLGGISTGER RRVSIAAQLL QDPKVMLFDE PTTGLDCMTA NQIVVLLVEL AR RNRIVVL TIHQPRSELF QLFDKIAILS FGELIFCGTP AEMLDFFNDC GYPCPEHSNP FDFYMDLTSV DTQSKEREIE TSK RVQMIE SAYKKSAICH KTLKNIERMK HLKTLPMVPF KTKDSPGVFS KLGVLLRRVT RNLVRNKLAV ITRLLQNLIM GLFL LFFVL RVRSNVLKGA IQDRVGLLYQ FVGATPYTGM LNAVNLFPVL RAVSDQESQD GLYQKWQMML AYALHVLPFS VVATM IFSS VCYWTLGLHP EVARFGYFSA ALLAPHLIGE FLTLVLLGIV QNPNIVNSVV ALLSIAGVLV GSGFLRNIQE MPIPFK IIS YFTFQKYCSE ILVVNEFYGL NFTCGSSNVS VTTNPMCAFT QGIQFIEKTC PGATSRFTMN FLILYSFIPA LVILGIV VF KIRDHLISRG SHHHHHHGHH HHHH |
-Macromolecule #2: ATP-binding cassette sub-family G member 8
Macromolecule | Name: ATP-binding cassette sub-family G member 8 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO EC number: Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 80.365828 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR DLNYQVDLAS QVPWFEQLAQ FKMPWTSPSC QNSCELGIQ NLSFKVRSGQ MLAIIGSSGC GRASLLDVIT GRGHGGKIKS GQIWINGQPS SPQLVRKCVA HVRQHNQLLP N LTVRETLA ...String: MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR DLNYQVDLAS QVPWFEQLAQ FKMPWTSPSC QNSCELGIQ NLSFKVRSGQ MLAIIGSSGC GRASLLDVIT GRGHGGKIKS GQIWINGQPS SPQLVRKCVA HVRQHNQLLP N LTVRETLA FIAQMRLPRT FSQAQRDKRV EDVIAELRLR QCADTRVGNM YVRGLSGGER RRVSIGVQLL WNPGILILDE PT SGLDSFT AHNLVKTLSR LAKGNRLVLI SLHQPRSDIF RLFDLVLLMT SGTPIYLGAA QHMVQYFTAI GYPCPRYSNP ADF YVDLTS IDRRSREQEL ATREKAQSLA ALFLEKVRDL DDFLWKAETK DLDEDTCVES SVTPLDTNCL PSPTKMPGAV QQFT TLIRR QISNDFRDLP TLLIHGAEAC LMSMTIGFLY FGHGSIQLSF MDTAALLFMI GALIPFNVIL DVISKCYSER AMLYY ELED GLYTTGPYFF AKILGELPEH CAYIIIYGMP TYWLANLRPG LQPFLLHFLL VWLVVFCCRI MALAAAALLP TFHMAS FFS NALYNSFYLA GGFMINLSSL WTVPAWISKV SFLRWCFEGL MKIQFSRRTY KMPLGNLTIA VSGDKILSVM ELDSYPL YA IYLIVIGLSG GFMVLYYVSL RFIKQKPSQD WASNSLEVLF QGPNVDSKRR WKKNFIAVSA ANRFKKISSS GAL |
-Macromolecule #3: 2C7 Fab heavy chain
Macromolecule | Name: 2C7 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.37967 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGWSCIILFL VATATGVHSE VKLVESGGGL VQPGGSLRLS CATSGFTFSE FFMEWVRQPP GKRLEWVAVS RNEANDYTTD YSASVKGRF IVSRDTSQNI LYLQMNALRA EDTAIYYCAR DAWMGFDYWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG T AALGCLVK ...String: MGWSCIILFL VATATGVHSE VKLVESGGGL VQPGGSLRLS CATSGFTFSE FFMEWVRQPP GKRLEWVAVS RNEANDYTTD YSASVKGRF IVSRDTSQNI LYLQMNALRA EDTAIYYCAR DAWMGFDYWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG T AALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KS CDKTH |
-Macromolecule #4: 2C7 Fab light chain
Macromolecule | Name: 2C7 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.605615 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGWSCIILFL VATARTGVHS DIQMTQSPSS LSASLGERVS LTCRASQEIS GYLSWLQQKP DGTIQRLIYA AFSLDSGVPK RFSGSRSGS DYSLTISSLE SEDLAHYYCL QYASYPCTFG GGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW ...String: MGWSCIILFL VATARTGVHS DIQMTQSPSS LSASLGERVS LTCRASQEIS GYLSWLQQKP DGTIQRLIYA AFSLDSGVPK RFSGSRSGS DYSLTISSLE SEDLAHYYCL QYASYPCTFG GGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #5: ERGOSTEROL
Macromolecule | Name: ERGOSTEROL / type: ligand / ID: 5 / Number of copies: 1 / Formula: ERG |
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Molecular weight | Theoretical: 396.648 Da |
Chemical component information | ![]() ChemComp-ERG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
Details | Added 8mM ATP, Magnesium and 0.2mg/ml cholesterol in ethanol |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 4900 / Average exposure time: 1.8 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |