5YE5

structure of endo-lysosomal TRPML1 channel inserting into nanodisc

Summary for 5YE5

• Entry DOI: 10.2210/pdb5ye5/pdb
• EMDB information: 6826
• Descriptor: mammalian endo-lysosomal TRPML1 channel, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: mtrpml1, mucolipidosis type iv, structual comparisons, combined regulation mechanism, membrane protein
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell membrane ; Multi-pass membrane protein : Q99J21
• Total number of polymer chains: 4
• Total formula weight: 264064.13

Authors

Yang, M.,Gao, N. (deposition date: 2017-09-15, release date: 2017-11-15, Last modification date: 2020-07-29)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (5.8 Å)