8UVB

Structure of NaCT-PF4a complex

Summary for 8UVB

• Entry DOI: 10.2210/pdb8uvb/pdb
• EMDB information: 42614 42620
• Descriptor: Solute carrier family 13 member 5, SODIUM ION, (2R)-2-hydroxy-2-[2-(2-methoxy-5-methylpyridin-3-yl)ethyl]butanedioic acid (3 entities in total)
• Functional Keywords: na(+)/citrate cotransporter(nact), solute carries, elevator type alternating access, membrane protein, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 126880.14

Authors

Li, Y.,Wang, D.N.,Mindell, J.A.,Rice, W.J.,Song, J.,Mikusevic, V.,Marden, J.J.,Becerril, A.,Kuang, H.,Wang, B. (deposition date: 2023-11-02, release date: 2024-12-25)

Primary citation

Li, Y.,Song, J.,Mikusevic, V.,Marden, J.J.,Becerril, A.,Kuang, H.,Wang, B.,Rice, W.J.,Mindell, J.A.,Wang, D.N.
Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C, outward-occluded C and inward-open C. A dicarboxylate is first bound and recognized in C and how the substrate interacts with NaDC3 in C likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the C state and modulates the kinetic barrier to the transport domain movement. Structural comparison of an inhibitor-bound structure of NaDC3 to that of the sodium-dependent citrate transporter suggests ways for making an inhibitor that is specific for NaDC3.

PubMed: 39622972
DOI: 10.1038/s41594-024-01433-0

Experimental method

ELECTRON MICROSCOPY (2.13 Å)