+Open data
-Basic information
Entry | Database: PDB / ID: 7lkp | |||||||||
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Title | Structure of ATP-free human ABCA4 | |||||||||
Components | Retinal-specific phospholipid-transporting ATPase ABCA4 | |||||||||
Keywords | TRANSLOCASE / ABC transporter / importer / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information rod photoreceptor disc membrane / flippase activity / N-retinylidene-phosphatidylethanolamine flippase activity / all-trans retinal binding / phospholipid transfer to membrane / retinol transmembrane transporter activity / phospholipid transporter activity / 11-cis retinal binding / retinal metabolic process / ATPase-coupled intramembrane lipid transporter activity ...rod photoreceptor disc membrane / flippase activity / N-retinylidene-phosphatidylethanolamine flippase activity / all-trans retinal binding / phospholipid transfer to membrane / retinol transmembrane transporter activity / phospholipid transporter activity / 11-cis retinal binding / retinal metabolic process / ATPase-coupled intramembrane lipid transporter activity / phosphatidylethanolamine flippase activity / phototransduction, visible light / retinoid binding / P-type phospholipid transporter / photoreceptor cell maintenance / phospholipid translocation / retinoid metabolic process / lipid transport / Retinoid cycle disease events / The canonical retinoid cycle in rods (twilight vision) / ATPase-coupled transmembrane transporter activity / photoreceptor outer segment / ABC-type transporter activity / visual perception / ABC-family proteins mediated transport / transmembrane transport / photoreceptor disc membrane / cytoplasmic vesicle / intracellular membrane-bounded organelle / GTPase activity / endoplasmic reticulum / ATP hydrolysis activity / ATP binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.27 Å | |||||||||
Authors | Liu, F. / Lee, J. / Chen, J. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Elife / Year: 2021 Title: Molecular structures of the eukaryotic retinal importer ABCA4. Authors: Fangyu Liu / James Lee / Jue Chen / Abstract: The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import) ...The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here, we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids. | |||||||||
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 | 7lkp.cif.gz | 364.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lkp.ent.gz | 297.6 KB | Display | PDB format |
PDBx/mmJSON format | 7lkp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lk/7lkp ftp://data.pdbj.org/pub/pdb/validation_reports/lk/7lkp | HTTPS FTP |
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-Related structure data
Related structure data | 23409MC 7lkzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10808 (Title: Cryo-electron microscopy reconstruction of ATP-free ABCA4 Data size: 1.9 TB Data #1: Unaligned and uncorrected multiframe movies of human ATP-free ABCA4 [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 256202.531 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCA4, ABCR / Production host: Homo sapiens (human) References: UniProt: P78363, P-type phospholipid transporter |
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-Sugars , 3 types, 8 molecules
#2: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...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 |
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#3: 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 |
#4: Sugar | ChemComp-NAG / |
-Non-polymers , 3 types, 15 molecules
#5: Chemical | ChemComp-CLR / #6: Chemical | ChemComp-POV / ( #7: Chemical | ChemComp-AJP / | |
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-Details
Has ligand of interest | N |
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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: ABCA4 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Conc.: 5.5 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 FIELDBright-field microscopy |
Image recording | Electron dose: 1.51 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18_3855: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 320102 / Symmetry type: POINT | ||||||||||||||||||||||||
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