8UVI

Structure of NaDC3-Succinate complex in Coo-Coo conformation

8UVI の概要

• エントリーDOI: 10.2210/pdb8uvi/pdb
• EMDBエントリー: 42615 42616 42617 42618 42619 42621
• 分子名称: Na(+)/dicarboxylate cotransporter 3, SODIUM ION, SUCCINIC ACID, ... (5 entities in total)
• 機能のキーワード: na(+)/dicarboxylate cotransporter(nadc3), solute carries, elevator type alternating access, membrane protein, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 140584.38

構造登録者

Li, Y.,Wang, D.N.,Mindell, J.A.,Rice, W.J.,Song, J.,Mikusevic, V.,Marden, J.J.,Becerril, A.,Kuang, H.,Wang, B. (登録日: 2023-11-03, 公開日: 2024-12-25, 最終更新日: 2025-04-02)

主引用文献

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., 32:502-512, 2025

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

実験手法

ELECTRON MICROSCOPY (2.53 Å)