6WC9

Human open state TMEM175 in KCl

6WC9 の概要

• エントリーDOI: 10.2210/pdb6wc9/pdb
• EMDBエントリー: 21603 21604 21605 21606
• 分子名称: Endosomal/lysosomal potassium channel TMEM175, POTASSIUM ION (3 entities in total)
• 機能のキーワード: ion channel, lysosome, potassium channel, 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: 111608.12

構造登録者

Oh, S.,Paknejad, N.,Hite, R.K. (登録日: 2020-03-30, 公開日: 2020-04-15, 最終更新日: 2024-03-06)

主引用文献

Oh, S.,Paknejad, N.,Hite, R.K.
Gating and selectivity mechanisms for the lysosomal K + channel TMEM175.
Elife, 9:-, 2020

PubMed Abstract: Transmembrane protein 175 (TMEM175) is a K-selective ion channel expressed in lysosomal membranes, where it establishes a membrane potential essential for lysosomal function and its dysregulation is associated with the development of Parkinson's Disease. TMEM175 is evolutionarily distinct from all known channels, predicting novel ion-selectivity and gating mechanisms. Here we present cryo-EM structures of human TMEM175 in open and closed conformations, enabled by resolutions up to 2.6 Å. Human TMEM175 adopts a homodimeric architecture with a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, these same residues establish a constriction essential for K selectivity. These studies reveal the mechanisms of permeation, selectivity and gating and lay the groundwork for understanding the role of TMEM175 in lysosomal function.

PubMed: 32228865
DOI: 10.7554/eLife.53430

実験手法

ELECTRON MICROSCOPY (2.64 Å)