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Yorodumi- PDB-7fdv: Cryo-EM structure of the human cholesterol transporter ABCG1 in c... -
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-Basic information
Entry | Database: PDB / ID: 7fdv | ||||||
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Title | Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol | ||||||
Components | ATP-binding cassette sub-family G member 1 | ||||||
Keywords | MEMBRANE PROTEIN / Human ABCG1 / cholsterol transporter / ATP-bound / cholesterol | ||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.26 Å | ||||||
Authors | Xu, D. / Li, Y.Y. / Yang, F.R. / Sun, C.R. / Pan, J.H. / Wang, L. / Chen, Z.P. / Fang, S.C. / Yao, X.B. / Hou, W.T. ...Xu, D. / Li, Y.Y. / Yang, F.R. / Sun, C.R. / Pan, J.H. / Wang, L. / Chen, Z.P. / Fang, S.C. / Yao, X.B. / Hou, W.T. / Zhou, C.Z. / Chen, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Rep / Year: 2022 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7fdv.cif.gz | 201 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7fdv.ent.gz | 158.1 KB | Display | PDB format |
PDBx/mmJSON format | 7fdv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7fdv_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7fdv_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7fdv_validation.xml.gz | 39.5 KB | Display | |
Data in CIF | 7fdv_validation.cif.gz | 55.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fd/7fdv ftp://data.pdbj.org/pub/pdb/validation_reports/fd/7fdv | HTTPS FTP |
-Related structure data
Related structure data | 31547MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 75670.844 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCG1, ABC8, WHT1 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) References: UniProt: P45844, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate #2: Chemical | #3: Chemical | #4: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: The complex of human ABCG1 with cholesterol and ATP / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.152 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 3.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 57.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.26 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 151593 / Symmetry type: POINT |
Atomic model building | B value: 142 / Protocol: AB INITIO MODEL |