7SMP

CryoEM structure of NKCC1 Bu-I

7SMP の概要

• エントリーDOI: 10.2210/pdb7smp/pdb
• EMDBエントリー: 25204
• 分子名称: Solute carrier family 12 member 2, 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid, POTASSIUM ION (3 entities in total)
• 機能のキーワード: cotransporter, dimer, ion, 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: 207798.29

構造登録者

Moseng, M.A. (登録日: 2021-10-26, 公開日: 2022-09-28, 最終更新日: 2025-05-21)

主引用文献

Moseng, M.A.,Su, C.C.,Rios, K.,Cui, M.,Lyu, M.,Glaza, P.,Klenotic, P.A.,Delpire, E.,Yu, E.W.
Inhibition mechanism of NKCC1 involves the carboxyl terminus and long-range conformational coupling.
Sci Adv, 8:eabq0952-eabq0952, 2022

PubMed Abstract: The Na-K-2Cl cotransporter-1 (NKCC1) is an electroneutral Na-dependent transporter responsible for simultaneously translocating Na, K, and Cl ions into cells. In human tissue, NKCC1 plays a critical role in regulating cytoplasmic volume, fluid intake, chloride homeostasis, and cell polarity. Here, we report four structures of human NKCC1 (hNKCC1), both in the absence and presence of loop diuretic (bumetanide or furosemide), using single-particle cryo-electron microscopy. These structures allow us to directly observe various novel conformations of the hNKCC1 dimer. They also reveal two drug-binding sites located at the transmembrane and cytosolic carboxyl-terminal domains, respectively. Together, our findings enable us to delineate an inhibition mechanism that involves a coupled movement between the cytosolic and transmembrane domains of hNKCC1.

PubMed: 36306358
DOI: 10.1126/sciadv.abq0952

実験手法

ELECTRON MICROSCOPY (3.28 Å)