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Open data
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Basic information
Entry | Database: PDB / ID: 8w6g | ||||||
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Title | NaDC1 with inhibitor ACA | ||||||
![]() | Solute carrier family 13 member 2 | ||||||
![]() | TRANSPORT PROTEIN / inhibitor / NaDC1 | ||||||
Function / homology | ![]() low-affinity sodium:dicarboxylate symporter activity / sodium:dicarboxylate symporter activity / fumarate transmembrane transporter activity / fumarate transport / Sodium-coupled sulphate, di- and tri-carboxylate transporters / alpha-ketoglutarate transmembrane transporter activity / alpha-ketoglutarate transport / succinate transmembrane transport / succinate transmembrane transporter activity / cellular response to lithium ion ...low-affinity sodium:dicarboxylate symporter activity / sodium:dicarboxylate symporter activity / fumarate transmembrane transporter activity / fumarate transport / Sodium-coupled sulphate, di- and tri-carboxylate transporters / alpha-ketoglutarate transmembrane transporter activity / alpha-ketoglutarate transport / succinate transmembrane transport / succinate transmembrane transporter activity / cellular response to lithium ion / apical plasma membrane / extracellular exosome / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Chi, X. / Chen, Y. / Li, Y. / Zhang, Y. / Shen, Y. / Chen, Y. / Wang, Z. / Yan, R. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism. Authors: Ximin Chi / Yiming Chen / Yaning Li / Lu Dai / Yuanyuan Zhang / Yaping Shen / Yun Chen / Tianhao Shi / Haonan Yang / Zilong Wang / Renhong Yan / ![]() Abstract: The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into sodium ion-sulfate cotransporters (NaSs) and sodium ion-di- and-tricarboxylate ...The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into sodium ion-sulfate cotransporters (NaSs) and sodium ion-di- and-tricarboxylate cotransporters (NaDCs). NaS1 and NaDC1 regulate sulfate homeostasis and oxidative metabolism, respectively. NaS1 deficiency affects murine growth and fertility, while NaDC1 affects urinary citrate and calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition and transport remain insufficiently characterized. In this study, we determined the cryo-electron microscopy structures of human NaS1, capturing inward-facing and combined inward-facing/outward-facing conformations within a dimer both in apo and sulfate-bound states. In addition, we elucidated NaDC1's outward-facing conformation, encompassing apo, citrate-bound, and -(-amylcinnamoyl) anthranilic acid (ACA) inhibitor-bound states. Structural scrutiny illuminates a detailed elevator mechanism driving conformational changes. Notably, the ACA inhibitor unexpectedly binds primarily anchored by transmembrane 2 (TM2), Loop 10, TM11, and TM6a proximate to the cytosolic membrane. Our findings provide crucial insights into SLC13 transport mechanisms, paving the way for future drug design. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 192.9 KB | Display | ![]() |
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PDB format | ![]() | 152.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 40.3 KB | Display | |
Data in CIF | ![]() | 58.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 37322MC ![]() 8w6cC ![]() 8w6dC ![]() 8w6hC ![]() 8w6nC ![]() 8w6oC ![]() 8w6tC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 65934.250 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Chemical | Mass: 337.412 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H23NO3 #3: Chemical | #4: Chemical | 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: NaDC1 in complex with inhibitor N-(p-amylcinnamoyl)anthranilic acid (ACA) Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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 defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 444389 / Symmetry type: POINT |