8W6C

CryoEM structure of NaDC1 with Citrate

8W6C の概要

• エントリーDOI: 10.2210/pdb8w6c/pdb
• EMDBエントリー: 37320
• 分子名称: Solute carrier family 13 member 2, SODIUM ION, CHOLESTEROL HEMISUCCINATE, ... (6 entities in total)
• 機能のキーワード: citrate, transporter, 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: 134728.16

構造登録者

Chi, X.,Chen, Y.,Li, Y.,Dai, L.,Zhang, Y.,Shen, Y.,Chen, Y.,Shi, T.,Yang, H.,Wang, Z.,Yan, R. (登録日: 2023-08-28, 公開日: 2024-04-17)

主引用文献

Chi, X.,Chen, Y.,Li, Y.,Dai, L.,Zhang, Y.,Shen, Y.,Chen, Y.,Shi, T.,Yang, H.,Wang, Z.,Yan, R.
Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism.
Sci Adv, 10:eadl3685-eadl3685, 2024

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 -(-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.

PubMed: 38552027
DOI: 10.1126/sciadv.adl3685

実験手法

ELECTRON MICROSCOPY (2.7 Å)