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Open data
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Basic information
Entry | Database: PDB / ID: 7jsk | ||||||||||||||||||||||||
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Title | Structure of the NaCT-Citrate complex | ||||||||||||||||||||||||
![]() | Solute carrier family 13 member 5 | ||||||||||||||||||||||||
![]() | MEMBRANE PROTEIN / Transporter | ||||||||||||||||||||||||
Function / homology | ![]() oxaloacetate transport / succinate transport / citrate transport / organic acid:sodium symporter activity / sodium:dicarboxylate symporter activity / citrate transmembrane transporter activity / fumarate transport / Sodium-coupled sulphate, di- and tri-carboxylate transporters / alpha-ketoglutarate transport / succinate transmembrane transporter activity ...oxaloacetate transport / succinate transport / citrate transport / organic acid:sodium symporter activity / sodium:dicarboxylate symporter activity / citrate transmembrane transporter activity / fumarate transport / Sodium-coupled sulphate, di- and tri-carboxylate transporters / alpha-ketoglutarate transport / succinate transmembrane transporter activity / monoatomic anion transmembrane transport / cellular response to lithium ion / membrane => GO:0016020 / nucleoplasm / identical protein binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | ||||||||||||||||||||||||
![]() | Sauer, D.B. / Wang, B. / Song, J. / Rice, W.J. / Wang, D.N. | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and inhibition mechanism of the human citrate transporter NaCT. Authors: David B Sauer / Jinmei Song / Bing Wang / Jacob K Hilton / Nathan K Karpowich / Joseph A Mindell / William J Rice / Da-Neng Wang / ![]() Abstract: Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor ...Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor-which binds to the same site as citrate-arrests the transport cycle of NaCT. The NaCT-inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity. Finally, the NaCT structures provide a framework for understanding how various mutations abolish the transport activity of NaCT in the brain and thereby cause epilepsy associated with mutations in SLC13A5 in newborns (which is known as SLC13A5-epilepsy). | ||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 313.9 KB | Display | ![]() |
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PDB format | ![]() | 266.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22457MC ![]() 7jsjC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Unaligned 0 degree tilt micrographs of NaCT-Citrate data collection 29jun2020 [micrographs - multiframe] Data #2: Unaligned 20 degree tilt micrographs of NaCT-Citrate data collection 29jun2020 [micrographs - multiframe] Data #3: Unaligned 40 degree tilt micrographs of NaCT-Citrate data collection 29jun2020 [micrographs - multiframe] Data #4: Unaligned 50 degree tilt micrographs of NaCT-Citrate data collection 04jul2020 [micrographs - multiframe] Data #5: Unaligned 40 degree tilt micrographs of NaCT-Citrate data collection 04jul2020 [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 63110.812 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Sugar | #3: Chemical | #4: Chemical | ChemComp-NA / 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 |
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Sample preparation
Component | Name: The NaCT-Citrate complex / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.125 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 1700 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Image recording | Average exposure time: 8 sec. / Electron dose: 57.71 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.18_3855: / Classification: refinement | |||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 563708 / Symmetry type: POINT | |||||||||||||||||||||||||||
Refine LS restraints |
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