+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24252 | |||||||||
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Title | Cryo-EM structure of MFSD2A | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information Synthesis of PC / lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / retina morphogenesis in camera-type eye / regulation of neuron projection arborization / fatty acid transmembrane transporter activity / lysophospholipid translocation ...Synthesis of PC / lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / retina morphogenesis in camera-type eye / regulation of neuron projection arborization / fatty acid transmembrane transporter activity / lysophospholipid translocation / photoreceptor cell morphogenesis / lysophospholipid:sodium symporter activity / lysophospholipid transport / photoreceptor cell outer segment organization / : / lipid transport across blood-brain barrier / very-low-density lipoprotein particle assembly / regulation of dendrite development / negative regulation of fatty acid beta-oxidation / retinal pigment epithelium development / positive regulation of triglyceride biosynthetic process / plasma membrane => GO:0005886 / establishment of blood-brain barrier / symporter activity / transcytosis / motor behavior / long-chain fatty acid transmembrane transporter activity / maintenance of blood-brain barrier / carbohydrate transport / regulation of multicellular organism growth / long-chain fatty acid transport / fatty acid transport / energy homeostasis / cellular response to starvation / cognition / hippocampus development / brain development / positive regulation of cell growth / endoplasmic reticulum membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Zhang J / Feng L | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2021 Title: Structure and mechanism of blood-brain-barrier lipid transporter MFSD2A. Authors: Chase A P Wood / Jinru Zhang / Deniz Aydin / Yan Xu / Benjamin J Andreone / Urs H Langen / Ron O Dror / Chenghua Gu / Liang Feng / Abstract: MFSD2A is a sodium-dependent lysophosphatidylcholine symporter that is responsible for the uptake of docosahexaenoic acid into the brain, which is crucial for the development and performance of the ...MFSD2A is a sodium-dependent lysophosphatidylcholine symporter that is responsible for the uptake of docosahexaenoic acid into the brain, which is crucial for the development and performance of the brain. Mutations that affect MFSD2A cause microcephaly syndromes. The ability of MFSD2A to transport lipid is also a key mechanism that underlies its function as an inhibitor of transcytosis to regulate the blood-brain barrier. Thus, MFSD2A represents an attractive target for modulating the permeability of the blood-brain barrier for drug delivery. Here we report the cryo-electron microscopy structure of mouse MFSD2A. Our structure defines the architecture of this important transporter, reveals its unique extracellular domain and uncovers its substrate-binding cavity. The structure-together with our functional studies and molecular dynamics simulations-identifies a conserved sodium-binding site, reveals a potential lipid entry pathway and helps to rationalize MFSD2A mutations that underlie microcephaly syndromes. These results shed light on the critical lipid transport function of MFSD2A and provide a framework to aid in the design of specific modulators for therapeutic purposes. | |||||||||
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_24252.map.gz | 43.5 MB | EMDB map data format | |
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Header (meta data) | emd-24252-v30.xml emd-24252.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24252_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_24252.png | 106.5 KB | ||
Others | emd_24252_half_map_1.map.gz emd_24252_half_map_2.map.gz | 36.8 MB 36.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24252 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24252 | HTTPS FTP |
-Validation report
Summary document | emd_24252_validation.pdf.gz | 709.6 KB | Display | EMDB validaton report |
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Full document | emd_24252_full_validation.pdf.gz | 709.2 KB | Display | |
Data in XML | emd_24252_validation.xml.gz | 14.1 KB | Display | |
Data in CIF | emd_24252_validation.cif.gz | 18.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24252 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24252 | HTTPS FTP |
-Related structure data
Related structure data | 7n98MC M: atomic model generated by this map C: citing same article (ref.) |
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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_24252.map.gz / Format: CCP4 / Size: 47.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_24252_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24252_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : membrane protein complex
Entire | Name: membrane protein complex |
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Components |
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-Supramolecule #1: membrane protein complex
Supramolecule | Name: membrane protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Macromolecule #1: Sodium-dependent lysophosphatidylcholine symporter 1
Macromolecule | Name: Sodium-dependent lysophosphatidylcholine symporter 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 59.038602 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAKGEGAESG SAAGLLPTSI LQASERPVQV KKEPKKKQQL SICNKLCYAV GGAPYQLTGC ALGFFLHIYL LDVAKVEPLP ASIILFVGR AWDAFTDPLV GFCISKSSWT RLGRLMPWII FSTPLAIIAY FLIWFVPDFP SGTESSHGFL WYLLFYCLFE T LVTCFHVP ...String: MAKGEGAESG SAAGLLPTSI LQASERPVQV KKEPKKKQQL SICNKLCYAV GGAPYQLTGC ALGFFLHIYL LDVAKVEPLP ASIILFVGR AWDAFTDPLV GFCISKSSWT RLGRLMPWII FSTPLAIIAY FLIWFVPDFP SGTESSHGFL WYLLFYCLFE T LVTCFHVP YSALTMFIST EQSERDSATA YRMTVEVLGT VIGTAIQGQI VGQAKAPCLQ DQNGSVVVSE VANRTQSTAS LK DTQNAYL LAAGIIASIY VLCAFILILG VREQRELYES QQAESMPFFQ GLRLVMGHGP YVKLIAGFLF TSLAFMLVEG NFA LFCTYT LDFRNEFQNL LLAIMLSATF TIPIWQWFLT RFGKKTAVYI GISSAVPFLI LVALMERNLI VTYVVAVAAG VSVA AAFLL PWSMLPDVID DFHLKHPHSP GTEPIFFSFY VFFTKFASGV SLGVSTLSLD FANYQRQGCS QPEQVKFTLK MLVTM APII LILLGLLLFK LYPIDEEKRR QNKKALQALR EEASSSGCSD TDSTELASIL |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/1 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 96 % / Chamber temperature: 293 K / Instrument: LEICA EM GP |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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 |