Substrate Translocation and Inhibition in Human Dicarboxylate Transporter NaDC3
- Description
High-affinity sodium–dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors, and signaling molecules. To understand the cellular signaling process and developing inhibitors requires knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. This study used single-particle cryo-electron microscopy to determine structures of NaDC3 in the presence of each of the three substrates: succinate, DMS and αKG. The dataset includes electron microscopy densities and protein models of NaDC3–succinate Coo–Coo, NaDC3–succinate Coo–Ci, NaDC3–DMS Co–Ci, NaDC3–DMS Ci–Ci, NaDC3–αKG Ci–Ci, NaDC3–PF4a Ci–Ci, NaCT–succinate Ci–Ci, and NaCT–PF4a Ci–Ci complexes. This helped determine the structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open Co, outward-occluded Coo, and inward-open Ci.
Access
- Restrictions
-
Free to All
- Instructions
- Electron microscopy densities and protein models were deposited to the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB).
- Grant Support
-
Simons Foundation/Simons FoundationTESS Research Foundation/TESS Research FoundationIntramural Research Program/National Institute of Neurological Disorders and StrokeG. Harold and Leila Y. Mathers Foundation/G. Harold and Leila Y. Mathers Foundation