7DYS

CryoEM structure of full length mouse TRPML2

7DYS の概要

• エントリーDOI: 10.2210/pdb7dys/pdb
• EMDBエントリー: 30924
• 分子名称: Mucolipin-2 (1 entity in total)
• 機能のキーワード: transient receptor potential mucolipin channels, trp channel, trpml2, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 240041.03

構造登録者

Song, X.J.,Li, J.,Duan, J.J.,Zhang, J. (登録日: 2021-01-22, 公開日: 2022-03-23, 最終更新日: 2025-06-25)

主引用文献

Song, X.,Li, J.,Tian, M.,Zhu, H.,Hu, X.,Zhang, Y.,Cao, Y.,Ye, H.,McCormick, P.J.,Zeng, B.,Fu, Y.,Duan, J.,Zhang, J.
Cryo-EM structure of mouse TRPML2 in lipid nanodiscs.
J.Biol.Chem., 298:101487-101487, 2022

PubMed Abstract: In mammalians, transient receptor potential mucolipin ion channels (TRPMLs) exhibit variable permeability to cations such as Ca, Fe, Zn, and Na and can be activated by the phosphoinositide PI(3,5)P2 in the endolysosomal system. Loss or dysfunction of TRPMLs has been implicated in lysosomal storage disorders, infectious diseases, and metabolic diseases. TRPML2 has recently been identified as a mechanosensitive and hypotonicity-sensitive channel in endolysosomal organelles, which distinguishes it from TRPML1 and TRPML3. However, the molecular and gating mechanism of TRPML2 remains elusive. Here, we present the cryo-EM structure of the full-length mouse TRPML2 in lipid nanodiscs at 3.14 Å resolution. The TRPML2 homotetramer structure at pH 7.4 in the apo state reveals an inactive conformation and some unique features of the extracytosolic/luminal domain and voltage sensor-like domain that have implications for the ion-conducting pathway. This structure enables new comparisons between the different subgroups of TRPML channels with available structures and provides structural insights into the conservation and diversity of TRPML channels. These comparisons have broad implications for understanding a variety of molecular mechanisms of TRPMLs in different pH conditions, including with and without bound agonists and antagonists.

PubMed: 34915027
DOI: 10.1016/j.jbc.2021.101487

実験手法

ELECTRON MICROSCOPY (3.18 Å)