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- EMDB-13118: Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-13118 | |||||||||
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Title | Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound | |||||||||
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Function / homology | ![]() ABC-type sterol transporter activity / glycoprotein transport / cellular response to high density lipoprotein particle stimulus / intracellular cholesterol transport / toxin transmembrane transporter activity / ABC transporters in lipid homeostasis / floppase activity / response to lipid / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity ...ABC-type sterol transporter activity / glycoprotein transport / cellular response to high density lipoprotein particle stimulus / intracellular cholesterol transport / toxin transmembrane transporter activity / ABC transporters in lipid homeostasis / floppase activity / response to lipid / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity / phospholipid homeostasis / high-density lipoprotein particle remodeling / phospholipid efflux / negative regulation of cholesterol storage / cholesterol transfer activity / reverse cholesterol transport / low-density lipoprotein particle remodeling / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / negative regulation of macrophage derived foam cell differentiation / HDL remodeling / cholesterol efflux / regulation of cholesterol metabolic process / positive regulation of cholesterol efflux / positive regulation of amyloid-beta formation / cholesterol binding / amyloid precursor protein catabolic process / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cholesterol metabolic process / cholesterol homeostasis / positive regulation of protein secretion / recycling endosome / phospholipid binding / transmembrane transport / ADP binding / endosome / protein heterodimerization activity / Golgi membrane / external side of plasma membrane / endoplasmic reticulum membrane / Golgi apparatus / protein homodimerization activity / ATP hydrolysis activity / mitochondrion / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
![]() | Skarda L / Kowal J / Locher KP | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the Human Cholesterol Transporter ABCG1. Authors: Liga Skarda / Julia Kowal / Kaspar P Locher / ![]() Abstract: ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. Despite its role in preventing lipid accumulation and the development of cardiovascular and ...ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. Despite its role in preventing lipid accumulation and the development of cardiovascular and metabolic disease, the mechanism underpinning ABCG1-mediated cholesterol transport is unknown. Here we report a cryo-EM structure of human ABCG1 at 4 Å resolution in an inward-open state, featuring sterol-like density in the binding cavity. Structural comparison with the multidrug transporter ABCG2 and the sterol transporter ABCG5/G8 reveals the basis of mechanistic differences and distinct substrate specificity. Benzamil and taurocholate inhibited the ATPase activity of liposome-reconstituted ABCG1, whereas the ABCG2 inhibitor Ko143 did not. Based on the structural insights into ABCG1, we propose a mechanism for ABCG1-mediated cholesterol transport. | |||||||||
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 | ![]() | 201.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.9 KB 11.9 KB | Display Display | ![]() |
Images | ![]() | 36.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7oz1MC 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: 0.66 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 : Human ABCG1 with bound ATP and CHS
Entire | Name: Human ABCG1 with bound ATP and CHS |
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Components |
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-Supramolecule #1: Human ABCG1 with bound ATP and CHS
Supramolecule | Name: Human ABCG1 with bound ATP and CHS / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Isoform 4 of ATP-binding cassette sub-family G member 1
Macromolecule | Name: Isoform 4 of ATP-binding cassette sub-family G member 1 type: protein_or_peptide / ID: 1 / Number of copies: 2 / 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: 75.658508 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MACLMAAFSV GTAMNASSYS AEMTEPKSVC VSVDEVVSSN MEATETDLLN GHLKKVDNNL TEAQRFSSLP RRAAVNIEFR DLSYSVPEG PWWRKKGYKT LLKGISGKFN SGELVAIMGP SGAGKSTLMN ILAGYRETGM KGAVLINGLP RDLRCFRKVS C YIMQDDML ...String: MACLMAAFSV GTAMNASSYS AEMTEPKSVC VSVDEVVSSN MEATETDLLN GHLKKVDNNL TEAQRFSSLP RRAAVNIEFR DLSYSVPEG PWWRKKGYKT LLKGISGKFN SGELVAIMGP SGAGKSTLMN ILAGYRETGM KGAVLINGLP RDLRCFRKVS C YIMQDDML LPHLTVQEAM MVSAHLKLQE KDEGRREMVK EILTALGLLS CANTRTGSLS GGQRKRLAIA LELVNNPPVM FF DQPTSGL DSASCFQVVS LMKGLAQGGR SIICTIHQPS AKLFELFDQL YVLSQGQCVY RGKVCNLVPY LRDLGLNCPT YHN PADFVM EVASGEYGDQ NSRLVRAVRE GMCDSDHKRD LGGDAEVNPF LWHRPSEEDS SSMEGCHSFS ASCLTQFCIL FKRT FLSIM RDSVLTHLRI TSHIGIGLLI GLLYLGIGNE AKKVLSNSGF LFFSMLFLMF AALMPTVLTF PLEMGVFLRE HLNYW YSLK AYYLAKTMAD VPFQIMFPVA YCSIVYWMTS QPSDAVRFVL FAALGTMTSL VAQSLGLLIG AASTSLQVAT FVGPVT AIP VLLFSGFFVS FDTIPTYLQW MSYISYVRYG FEGVILSIYG LDREDLHCDI DETCHFQKSE AILRELDVEN AKLYLDF IV LGIFFISLRL IAYFVLRYKI RAERSSRVDT ETSQVAPA |
-Macromolecule #2: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 2 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Macromolecule #3: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 8 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #4: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
Macromolecule | Name: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / type: ligand / ID: 4 / Number of copies: 2 / Formula: PEE |
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Molecular weight | Theoretical: 744.034 Da |
Chemical component information | ![]() ChemComp-PEE: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277.0 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 17524 / Average electron dose: 1.76 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 39791 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |