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- EMDB-31547: Cryo-EM structure of the human cholesterol transporter ABCG1 in c... -
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Open data
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Basic information
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Title | Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol | |||||||||
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![]() | Human ABCG1 / cholsterol transporter / ATP-bound / cholesterol / MEMBRANE PROTEIN | |||||||||
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 / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity / phospholipid homeostasis ...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 / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity / phospholipid homeostasis / high-density lipoprotein particle remodeling / phospholipid efflux / reverse cholesterol transport / cholesterol transfer activity / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / low-density lipoprotein particle remodeling / HDL remodeling / cholesterol efflux / regulation of cholesterol metabolic process / positive regulation of amyloid-beta formation / response to lipid / cholesterol binding / negative regulation of cholesterol storage / amyloid precursor protein catabolic process / negative regulation of macrophage derived foam cell differentiation / positive regulation of cholesterol efflux / 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 / external side of plasma membrane / Golgi 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: 3.26 Å | |||||||||
![]() | Xu D / Li YY / Yang FR / Sun CR / Pan JH / Wang L / Chen ZP / Fang SC / Yao XB / Hou WT ...Xu D / Li YY / Yang FR / Sun CR / Pan JH / Wang L / Chen ZP / Fang SC / Yao XB / Hou WT / Zhou CZ / Chen Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and transport mechanism of the human cholesterol transporter ABCG1. Authors: Da Xu / Yanyan Li / Fengrui Yang / Cai-Rong Sun / Jinheng Pan / Liang Wang / Zhi-Peng Chen / Shu-Cheng Fang / Xuebiao Yao / Wen-Tao Hou / Cong-Zhao Zhou / Yuxing Chen / ![]() Abstract: The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this ...The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this pathway, the ATP-binding cassette transporter ABCG1 forwards cellular cholesterol to the extracellular acceptor nascent high-density lipoprotein (HDL). Here, we report a 3.26-Å cryo-electron microscopy structure of cholesterol-bound ABCG1 in an inward-facing conformation, which represents a turnover condition upon ATP binding. Structural analyses combined with functional assays reveals that a cluster of conserved hydrophobic residues, in addition to two sphingomyelins, constitute a well-defined cholesterol-binding cavity. The exit of this cavity is closed by three pairs of conserved Phe residues, which constitute a hydrophobic path for the release of cholesterol in an acceptor concentration-dependent manner. Overall, we propose an ABCG1-driven cholesterol transport cycle initiated by sphingomyelin-assisted cholesterol recruitment and accomplished by the release of cholesterol to HDL. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 49.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.4 KB 12.4 KB | Display Display | ![]() |
Images | ![]() | 34.1 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 514 KB | Display | ![]() |
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Full document | ![]() | 513.6 KB | Display | |
Data in XML | ![]() | 6.1 KB | Display | |
Data in CIF | ![]() | 6.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7fdvMC 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: 1.01 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 : The complex of human ABCG1 with cholesterol and ATP
Entire | Name: The complex of human ABCG1 with cholesterol and ATP |
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Components |
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-Supramolecule #1: The complex of human ABCG1 with cholesterol and ATP
Supramolecule | Name: The complex of human ABCG1 with cholesterol and ATP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 152 KDa |
-Macromolecule #1: ATP-binding cassette sub-family G member 1
Macromolecule | Name: 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: 75.670844 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 LWHRPSEEVK QTKRLKGLRK DSSSMEGCHS FSAS CLTQF CILFKRTFLS IMRDSVLTHL RITSHIGIGL LIGLLYLGIG NEAKKVLSNS GFLFFSMLFL MFAALMPTVL TFPLE MGVF LREHLNYWYS LKAYYLAKTM ADVPFQIMFP VAYCSIVYWM TSQPSDAVRF VLFAALGTMT SLVAQSLGLL IGAAST SLQ VATFVGPVTA IPVLLFSGFF VSFDTIPTYL QWMSYISYVR YGFEGVILSI YGLDREDLHC DIDETCHFQK SEAILRE LD VENAKLYLDF IVLGIFFISL RLIAYFVLRY KIRAER UniProtKB: ATP-binding cassette sub-family G member 1 |
-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: [(E,2S,3R)-2-(hexadecanoylamino)-3-oxidanyl-octadec-4-enyl] 2-(tr...
Macromolecule | Name: [(E,2S,3R)-2-(hexadecanoylamino)-3-oxidanyl-octadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate type: ligand / ID: 3 / Number of copies: 2 / Formula: HWP |
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Molecular weight | Theoretical: 703.028 Da |
Chemical component information | ![]() ChemComp-HWP: |
-Macromolecule #4: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3.5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 10 sec. / Pretreatment - Atmosphere: OTHER |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
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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: 57.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.26 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 151593 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL / Overall B value: 142 |
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Output model | ![]() PDB-7fdv: |