9DNX

Human ClC-3:TMEM9, TMEM9 Protomer A and B: Complete

これはPDB形式変換不可エントリーです。

9DNX の概要

• エントリーDOI: 10.2210/pdb9dnx/pdb
• EMDBエントリー: 47067
• 分子名称: H(+)/Cl(-) exchange transporter 3, Proton-transporting V-type ATPase complex assembly regulator TMEM9, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: ion channel, membrane protein, lysosomal protein, clc
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 227090.43

構造登録者

Son, Y.,Schrecker, M.,Hite, R.K. (登録日: 2024-09-18, 公開日: 2025-04-02, 最終更新日: 2025-10-29)

主引用文献

Schrecker, M.,Son, Y.,Planells-Cases, R.,Kar, S.,Vorobeva, V.,Schulte, U.,Fakler, B.,Jentsch, T.J.,Hite, R.K.
Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)P 2 .
Nat.Struct.Mol.Biol., 32:1972-1979, 2025

PubMed Abstract: The trafficking and activity of endosomes relies on the exchange of chloride ions and protons by members of the CLC family of chloride channels and transporters; mutations of the genes encoding these transporters are associated with numerous diseases. Despite their critical roles, the mechanisms by which CLC transporters are regulated are poorly understood. Here we show that two related accessory β-subunits, TMEM9 and TMEM9B, directly interact with ClC-3, ClC-4 and ClC-5. Cryo-electron microscopy structures reveal that TMEM9 inhibits ClC-3 by sealing the cytosolic entrance to the Cl ion pathway. Unexpectedly, we find that phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P) stabilizes the interaction between TMEM9 and ClC-3 and is required for proper regulation of ClC-3 by TMEM9. Collectively, our findings reveal that TMEM9 and PtdIns(3,5)P collaborate to regulate endosomal ion homeostasis by modulating the activity of ClC-3.

PubMed: 40670814
DOI: 10.1038/s41594-025-01617-2

実験手法

ELECTRON MICROSCOPY (2.86 Å)