+Open data
-Basic information
Entry | Database: PDB / ID: 5xjy | |||||||||
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Title | Cryo-EM structure of human ABCA1 | |||||||||
Components | ATP-binding cassette sub-family A member 1 | |||||||||
Keywords | TRANSPORT PROTEIN / membrane transporter | |||||||||
Function / homology | Function and homology information sphingolipid floppase activity / regulation of high-density lipoprotein particle assembly / apolipoprotein A-I receptor activity / positive regulation of high-density lipoprotein particle assembly / Defective ABCA1 causes TGD / signal release / response to vitamin B3 / apolipoprotein A-I binding / platelet dense granule organization / intracellular cholesterol transport ...sphingolipid floppase activity / regulation of high-density lipoprotein particle assembly / apolipoprotein A-I receptor activity / positive regulation of high-density lipoprotein particle assembly / Defective ABCA1 causes TGD / signal release / response to vitamin B3 / apolipoprotein A-I binding / platelet dense granule organization / intracellular cholesterol transport / high-density lipoprotein particle binding / phospholipid transporter activity / response to laminar fluid shear stress / protein transmembrane transport / floppase activity / HDL assembly / intracellular vesicle / phosphatidylserine floppase activity / cellular response to cholesterol / peptide secretion / phosphatidylcholine floppase activity / phospholipid homeostasis / phosphatidylcholine binding / phospholipid efflux / negative regulation of cholesterol storage / cholesterol transfer activity / reverse cholesterol transport / export across plasma membrane / high-density lipoprotein particle assembly / lipoprotein biosynthetic process / P-type phospholipid transporter / regulation of Cdc42 protein signal transduction / negative regulation of macrophage derived foam cell differentiation / syntaxin binding / cellular response to low-density lipoprotein particle stimulus / phospholipid translocation / cholesterol efflux / endosomal transport / positive regulation of cholesterol efflux / cholesterol binding / lysosome organization / phagocytosis, engulfment / cellular response to cytokine stimulus / apolipoprotein binding / endocytic vesicle / protein transmembrane transporter activity / protein secretion / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / cellular response to retinoic acid / phagocytic vesicle / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cholesterol metabolic process / cholesterol homeostasis / PPARA activates gene expression / adenylate cyclase-activating G protein-coupled receptor signaling pathway / small GTPase binding / cellular response to xenobiotic stimulus / ATPase binding / basolateral plasma membrane / cellular response to lipopolysaccharide / endosome / membrane raft / G protein-coupled receptor signaling pathway / external side of plasma membrane / intracellular membrane-bounded organelle / signaling receptor binding / endoplasmic reticulum membrane / perinuclear region of cytoplasm / Golgi apparatus / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Qian, H.W. / Yan, N. / Gong, X. | |||||||||
Funding support | China, 2items
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Citation | Journal: Cell / Year: 2017 Title: Structure of the Human Lipid Exporter ABCA1. Authors: Hongwu Qian / Xin Zhao / Pingping Cao / Jianlin Lei / Nieng Yan / Xin Gong / Abstract: ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of ...ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL deficiency. Here, we report the cryo-EM structure of human ABCA1 with nominal resolutions of 4.1 Å for the overall structure and 3.9 Å for the massive extracellular domain. The nucleotide-binding domains (NBDs) display a nucleotide-free state, while the two transmembrane domains (TMDs) contact each other through a narrow interface in the intracellular leaflet of the membrane. In addition to TMDs and NBDs, two extracellular domains of ABCA1 enclose an elongated hydrophobic tunnel. Structural mapping of dozens of disease-related mutations allows potential interpretation of their diverse pathogenic mechanisms. Structural-based analysis suggests a plausible "lateral access" mechanism for ABCA1-mediated lipid export that may be distinct from the conventional alternating-access paradigm. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5xjy.cif.gz | 326.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5xjy.ent.gz | 244 KB | Display | PDB format |
PDBx/mmJSON format | 5xjy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5xjy_validation.pdf.gz | 966 KB | Display | wwPDB validaton report |
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Full document | 5xjy_full_validation.pdf.gz | 986.1 KB | Display | |
Data in XML | 5xjy_validation.xml.gz | 52.6 KB | Display | |
Data in CIF | 5xjy_validation.cif.gz | 80.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xj/5xjy ftp://data.pdbj.org/pub/pdb/validation_reports/xj/5xjy | HTTPS FTP |
-Related structure data
Related structure data | 6724MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10798 (Title: Cryo-EM micrographs of human ABCA1 / Data size: 16.3 TB Data #1: The micrographs are the movie stacks (32 frames) after motion corrected with MotionCorr and binned 2-fold, resulting in a pixel size of 1.307 Å/pixel. [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 259512.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCA1, ABC1, CERP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O95477 |
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#2: Polysaccharide | beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#4: Sugar | ChemComp-NAG / |
-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: Membrane protein / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.11rc3_2542: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 790156 / Symmetry type: POINT | ||||||||||||||||||||||||
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