5YE5

structure of endo-lysosomal TRPML1 channel inserting into nanodisc

5YE5 の概要

• エントリーDOI: 10.2210/pdb5ye5/pdb
• EMDBエントリー: 6826
• 分子名称: mammalian endo-lysosomal TRPML1 channel, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: mtrpml1, mucolipidosis type iv, structual comparisons, combined regulation mechanism, membrane protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : Q99J21
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 264064.13

構造登録者

Yang, M.,Gao, N. (登録日: 2017-09-15, 公開日: 2017-11-15, 最終更新日: 2020-07-29)

主引用文献

Zhang, S.,Li, N.,Zeng, W.,Gao, N.,Yang, M.
Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism
Protein Cell, 8:834-847, 2017

PubMed Abstract: TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a "move upward" motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.

PubMed: 28936784
DOI: 10.1007/s13238-017-0476-5

実験手法

ELECTRON MICROSCOPY (5.8 Å)