7TTH

Human potassium-chloride cotransporter 1 in inward-open state

7TTH の概要

• エントリーDOI: 10.2210/pdb7tth/pdb
• EMDBエントリー: 26115 26116
• 分子名称: Solute carrier family 12 member 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, POTASSIUM ION (3 entities in total)
• 機能のキーワード: slc12a4, potassium-chloride transport, inward-open state, 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: 243316.78

構造登録者

Zhao, Y.X.,Cao, E.H. (登録日: 2022-02-01, 公開日: 2022-06-29, 最終更新日: 2025-05-28)

主引用文献

Zhao, Y.,Shen, J.,Wang, Q.,Ruiz Munevar, M.J.,Vidossich, P.,De Vivo, M.,Zhou, M.,Cao, E.
Structure of the human cation-chloride cotransport KCC1 in an outward-open state.
Proc.Natl.Acad.Sci.USA, 119:e2109083119-e2109083119, 2022

PubMed Abstract: Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl with Na and/or K across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K-Cl cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

PubMed: 35759661
DOI: 10.1073/pnas.2109083119

実験手法

ELECTRON MICROSCOPY (3.25 Å)