+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | NaS1 in IN/OUT state | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | NaS1 / IN/OUT state / apo state / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() sodium:sulfate symporter activity / monoatomic anion:sodium symporter activity / Sodium-coupled sulphate, di- and tri-carboxylate transporters / sulfate transport / sodium ion transport / transmembrane transport / apical plasma membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Chi X / Chen Y / Li Y / Zhang Y / Shen Y / Wang Z / Yan R | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 49.8 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 13.8 KB 13.8 KB | Display Display | ![]() |
Images | ![]() | 93.8 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Others | ![]() ![]() | 48.9 MB 48.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8w6tMC ![]() 8w6cC ![]() 8w6dC ![]() 8w6gC ![]() 8w6hC ![]() 8w6nC ![]() 8w6oC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_37332_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_37332_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Dimer of NaS1 in IN/OUT state
Entire | Name: Dimer of NaS1 in IN/OUT state |
---|---|
Components |
|
-Supramolecule #1: Dimer of NaS1 in IN/OUT state
Supramolecule | Name: Dimer of NaS1 in IN/OUT state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Solute carrier family 13 member 1
Macromolecule | Name: Solute carrier family 13 member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 67.68543 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MADYKDDDDK SGRMKFFSYI LVYRRFLFVV FTVLVLLPLP IVLHTKEAEC AYTLFVVATF WLTEALPLSV TALLPSLMLP MFGIMPSKK VASAYFKDFH LLLIGVICLA TSIEKWNLHK RIALKMVMMV GVNPAWLTLG FMSSTAFLSM WLSNTSTAAM V MPIAEAVV ...String: MADYKDDDDK SGRMKFFSYI LVYRRFLFVV FTVLVLLPLP IVLHTKEAEC AYTLFVVATF WLTEALPLSV TALLPSLMLP MFGIMPSKK VASAYFKDFH LLLIGVICLA TSIEKWNLHK RIALKMVMMV GVNPAWLTLG FMSSTAFLSM WLSNTSTAAM V MPIAEAVV QQIINAEAEV EATQMTYFNG STNHGLEIDE SVNGHEINER KEKTKPVPGY NNDTGKISSK VELEKNSGMR TK YRTKKGH VTRKLTCLCI AYSSTIGGLT TITGTSTNLI FAEYFNTRYP DCRCLNFGSW FTFSFPAALI ILLLSWIWLQ WLF LGFNFK EMFKCGKTKT VQQKACAEVI KQEYQKLGPI RYQEIVTLVL FIIMALLWFS RDPGFVPGWS ALFSEYPGFA TDST VALLI GLLFFLIPAK TLTKTTPTGE IVAFDYSPLI TWKEFQSFMP WDIAILVGGG FALADGCEES GLSKWIGNKL SPLGS LPAW LIILISSLMV TSLTEVASNP ATITLFLPIL SPLAEAIHVN PLYILIPSTL CTSFAFLLPV ANPPNAIVFS YGHLKV IDM VKAGLGVNIV GVAVVMLGIC TWIVPMFDLY TYPSWAPAMS NETMP UniProtKB: Solute carrier family 13 member 1 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: NONE |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 169571 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |