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Yorodumi- EMDB-24657: Cryo-EM Structure of Nanodisc reconstituted ABCD1 in inward open ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24657 | |||||||||
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Title | Cryo-EM Structure of Nanodisc reconstituted ABCD1 in inward open conformation | |||||||||
Map data | Nanodisc Reconstituted ABCD1 in inward open conformation | |||||||||
Sample |
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Keywords | VLCFA ABC transporter ABCD1 / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information ABC-type fatty-acyl-CoA transporter activity / peroxisomal membrane transport / very long-chain fatty-acyl-CoA catabolic process / very long-chain fatty acyl-CoA hydrolase activity / positive regulation of unsaturated fatty acid biosynthetic process / Linoleic acid (LA) metabolism / Defective ABCD1 causes ALD / alpha-linolenic acid metabolic process / long-chain fatty acid catabolic process / alpha-linolenic acid (ALA) metabolism ...ABC-type fatty-acyl-CoA transporter activity / peroxisomal membrane transport / very long-chain fatty-acyl-CoA catabolic process / very long-chain fatty acyl-CoA hydrolase activity / positive regulation of unsaturated fatty acid biosynthetic process / Linoleic acid (LA) metabolism / Defective ABCD1 causes ALD / alpha-linolenic acid metabolic process / long-chain fatty acid catabolic process / alpha-linolenic acid (ALA) metabolism / long-chain fatty acid import into peroxisome / very long-chain fatty acid catabolic process / Beta-oxidation of very long chain fatty acids / regulation of fatty acid beta-oxidation / very long-chain fatty acid metabolic process / sterol homeostasis / Class I peroxisomal membrane protein import / peroxisome organization / regulation of mitochondrial depolarization / fatty acyl-CoA hydrolase activity / ABC transporters in lipid homeostasis / myelin maintenance / regulation of cellular response to oxidative stress / Hydrolases; Acting on ester bonds; Thioester hydrolases / positive regulation of fatty acid beta-oxidation / linoleic acid metabolic process / regulation of oxidative phosphorylation / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / fatty acid elongation / peroxisomal membrane / long-chain fatty acid transmembrane transporter activity / fatty acid beta-oxidation / ATPase-coupled transmembrane transporter activity / negative regulation of cytokine production involved in inflammatory response / fatty acid homeostasis / negative regulation of reactive oxygen species biosynthetic process / neuron projection maintenance / mitochondrial membrane / ADP binding / peroxisome / protein heterodimerization activity / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / protein homodimerization activity / ATP hydrolysis activity / ATP binding / identical protein binding / membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Alam A / Le LTM | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Commun Biol / Year: 2022 Title: Structures of the human peroxisomal fatty acid transporter ABCD1 in a lipid environment. Authors: Le Thi My Le / James Robert Thompson / Phuoc Xuan Dang / Janarjan Bhandari / Amer Alam / Abstract: The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to fatty acid catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, ...The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to fatty acid catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, progressive demyelination, and neurological impairments including X-linked adrenoleukodystrophy (X-ALD). We present cryo-EM structures of ABCD1 in phospholipid nanodiscs in a nucleotide bound conformation open to the peroxisomal lumen and an inward facing conformation open to the cytosol at up to 3.5 Å resolution, revealing details of its transmembrane cavity and ATP dependent conformational spectrum. We identify features distinguishing ABCD1 from its closest homologs and show that coenzyme A (CoA) esters of VLCFAs modulate ABCD1 activity in a species dependent manner. Our data suggest a transport mechanism where the CoA moieties of VLCFA-CoAs enter the hydrophilic transmembrane domain while the acyl chains extend out into the surrounding membrane bilayer. The structures help rationalize disease causing mutations and may aid ABCD1 targeted structure-based drug design. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_24657.map.gz | 20.8 MB | EMDB map data format | |
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Header (meta data) | emd-24657-v30.xml emd-24657.xml | 13.3 KB 13.3 KB | Display Display | EMDB header |
Images | emd_24657.png | 94.3 KB | ||
Filedesc metadata | emd-24657.cif.gz | 6.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24657 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24657 | HTTPS FTP |
-Validation report
Summary document | emd_24657_validation.pdf.gz | 537.3 KB | Display | EMDB validaton report |
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Full document | emd_24657_full_validation.pdf.gz | 536.8 KB | Display | |
Data in XML | emd_24657_validation.xml.gz | 5.5 KB | Display | |
Data in CIF | emd_24657_validation.cif.gz | 6.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24657 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24657 | HTTPS FTP |
-Related structure data
Related structure data | 7rraMC 7rr9C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_24657.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Nanodisc Reconstituted ABCD1 in inward open conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.79 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Human ABCD1 in Porcine BPL/Ch/MSP1D1 nanodiscs in Conformation op...
Entire | Name: Human ABCD1 in Porcine BPL/Ch/MSP1D1 nanodiscs in Conformation open to cytoplasm (Inward open) |
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Components |
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-Supramolecule #1: Human ABCD1 in Porcine BPL/Ch/MSP1D1 nanodiscs in Conformation op...
Supramolecule | Name: Human ABCD1 in Porcine BPL/Ch/MSP1D1 nanodiscs in Conformation open to cytoplasm (Inward open) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Human ABCD1 recombinantly expressed in HEK293 TREX cell line and reconstituted in MSP1D1 nanodiscs comprising 4:1 mixture of Porcine Brain Polar Lipids:Cholesterol. The reported molecular ...Details: Human ABCD1 recombinantly expressed in HEK293 TREX cell line and reconstituted in MSP1D1 nanodiscs comprising 4:1 mixture of Porcine Brain Polar Lipids:Cholesterol. The reported molecular weight of 0.0829 MDa is for the monomer. The assembly is a homodimer. The dimer was confirmed using SEC. |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 82.9 KDa |
-Macromolecule #1: ATP-binding cassette sub-family D member 1
Macromolecule | Name: ATP-binding cassette sub-family D member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: ec: 7.6.2.4 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 83.040867 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPVLSRPRPW RGNTLKRTAV LLALAAYGAH KVYPLVRQCL APARGLQAPA GEPTQEASGV AAAKAGMNRV FLQRLLWLLR LLFPRVLCR ETGLLALHSA ALVSRTFLSV YVARLDGRLA RCIVRKDPRA FGWQLLQWLL IALPATFVNS AIRYLEGQLA L SFRSRLVA ...String: MPVLSRPRPW RGNTLKRTAV LLALAAYGAH KVYPLVRQCL APARGLQAPA GEPTQEASGV AAAKAGMNRV FLQRLLWLLR LLFPRVLCR ETGLLALHSA ALVSRTFLSV YVARLDGRLA RCIVRKDPRA FGWQLLQWLL IALPATFVNS AIRYLEGQLA L SFRSRLVA HAYRLYFSQQ TYYRVSNMDG RLRNPDQSLT EDVVAFAASV AHLYSNLTKP LLDVAVTSYT LLRAARSRGA GT AWPSAIA GLVVFLTANV LRAFSPKFGE LVAEEARRKG ELRYMHSRVV ANSEEIAFYG GHEVELALLQ RSYQDLASQI NLI LLERLW YVMLEQFLMK YVWSASGLLM VAVPIITATG YSESDAEAVK KAALEKKEEE LVSERTEAFT IARNLLTAAA DAIE RIMSS YKEVTELAGY TARVHEMFQV FEDVQRCHFK RPRELEDAQA GSGTIGRSGV RVEGPLKIRG QVVDVEQGII CENIP IVTP SGEVVVASLN IRVEEGMHLL ITGPNGCGKS SLFRILGGLW PTYGGVLYKP PPQRMFYIPQ RPYMSVGSLR DQVIYP DSV EDMQRKGYSE QDLEAILDVV HLHHILQREG GWEAMCDWKD VLSGGEKQRI GMARMFYHRP KYALLDECTS AVSIDVE GK IFQAAKDAGI ALLSITHRPS LWKYHTHLLQ FDGEGGWKFE KLDSAARLSL TEEKQRLEQQ LAGIPKMQRR LQELCQIL G EAVAPAHVPA PSPQGPGGLQ GAST UniProtKB: ATP-binding cassette sub-family D member 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.5 mg/mL |
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Buffer | pH: 7.5 Details: 25mM HEPES pH 7.5, 150mM NaCl, 5mM ATP gammaS, 10mM Magnesium Chloride |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Average exposure time: 60.0 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |