8W6C

CryoEM structure of NaDC1 with Citrate


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.70 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism.

Chi, X.Chen, Y.Li, Y.Dai, L.Zhang, Y.Shen, Y.Chen, Y.Shi, T.Yang, H.Wang, Z.Yan, R.

(2024) Sci Adv 10: eadl3685-eadl3685

  • DOI: https://doi.org/10.1126/sciadv.adl3685
  • Primary Citation of Related Structures:  
    8W6C, 8W6D, 8W6G, 8W6H, 8W6N, 8W6O, 8W6T

  • PubMed 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 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 N -( p -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.


  • Organizational Affiliation

    State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Science, Xiamen University, Xiamen 361102, Fujian Province, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Solute carrier family 13 member 2
A, B
605Homo sapiensMutation(s): 0 
Gene Names: SLC13A2NADC1SDCT1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13183 (Homo sapiens)
Explore Q13183 
Go to UniProtKB:  Q13183
PHAROS:  Q13183
GTEx:  ENSG00000007216 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13183
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3PH (Subject of Investigation/LOI)
Query on 3PH

Download Ideal Coordinates CCD File 
H [auth A],
I [auth B]
1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE
C39 H77 O8 P
YFWHNAWEOZTIPI-DIPNUNPCSA-N
Y01
Query on Y01

Download Ideal Coordinates CCD File 
E [auth A],
G [auth A]
CHOLESTEROL HEMISUCCINATE
C31 H50 O4
WLNARFZDISHUGS-MIXBDBMTSA-N
CIT (Subject of Investigation/LOI)
Query on CIT

Download Ideal Coordinates CCD File 
F [auth A],
L [auth B]
CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
NA (Subject of Investigation/LOI)
Query on NA

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
J [auth B],
K [auth B]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.70 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Science Foundation (NSF, China)China32100975

Revision History  (Full details and data files)

  • Version 1.0: 2024-04-17
    Type: Initial release