|Entry||Database: PDB / ID: 5ydz|
|Title||structure of endo-lysosomal TRPML1 channel inserting into amphipol: state 1|
|Components||mammalian endo-lysosomal TRPML1 channel|
|Keywords||MEMBRANE PROTEIN / mTRPML1 / mucolipidosis type IV / structual comparisons / combined regulation mechanism|
|Function/homology||Transferrin endocytosis and recycling / cation transmembrane transport / intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity / ligand-gated calcium channel activity / NAADP-sensitive calcium-release channel activity / TRP channels / cellular response to pH / Polycystin cation channel, PKD1/PKD2 / Polycystin cation channel / cation channel activity ...Transferrin endocytosis and recycling / cation transmembrane transport / intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity / ligand-gated calcium channel activity / NAADP-sensitive calcium-release channel activity / TRP channels / cellular response to pH / Polycystin cation channel, PKD1/PKD2 / Polycystin cation channel / cation channel activity / phagocytic cup / autophagosome maturation / late endosome membrane / calcium ion transmembrane transport / cell projection / cellular response to calcium ion / endosomal transport / lysosomal membrane / phagocytic vesicle membrane / late endosome / adaptive immune response / protein homotetramerization / receptor complex / lysosome / lipid binding / membrane / integral component of membrane / plasma membrane / cytosol / Mucolipin-1|
Function and homology information
|Specimen source||Mus musculus / House mouse / mammal /|
|Method||Electron microscopy (5.8 Å resolution / Particle / Single particle) / Transmission electron microscopy|
|Authors||Yang, M. / Gao, N.|
|Citation||Journal: Protein Cell / Year: 2017|
Title: Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism.
Authors: Sensen Zhang / Ningning Li / Wenwen Zeng / Ning Gao / Maojun Yang
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 ...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.
SummaryFull reportAbout validation report
|Date||Deposition: Sep 15, 2017 / Release: Dec 27, 2017|
Downloads & links
A: mammalian endo-lysosomal TRPML1 channel
B: mammalian endo-lysosomal TRPML1 channel
C: mammalian endo-lysosomal TRPML1 channel
D: mammalian endo-lysosomal TRPML1 channel
Mass: 65573.617 Da / Num. of mol.: 4 / Source: (gene. exp.) Mus musculus / House mouse / mammal / / Gene: Mcoln1 / Production host: Homo sapiens / References: UniProt:Q99J21
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: SINGLE PARTICLE|
|Component||Name: mammalian endo-lysosomal TRPML1 channel inserting into amphipol|
Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: 1 / Source: RECOMBINANT
|Source (natural)||Organism: Mus musculus|
|Source (recombinant)||Organism: Homo sapiens|
|Buffer solution||pH: 7.4|
|Specimen||Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|EM embedding||Material: Amorphous ice|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELD|
|Image recording||Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|EM software||Name: RELION / Version: 2 / Category: RECONSTRUCTION|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Symmetry||Point symmetry: C4|
|3D reconstruction||Resolution: 5.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 167000 / Symmetry type: POINT|
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