5YE1

structure of endo-lysosomal TRPML1 channel inserting into amphipol: state 2


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism

Zhang, S.Li, N.Zeng, W.Gao, N.Yang, M.

(2017) Protein Cell 8: 834-847

  • DOI: https://doi.org/10.1007/s13238-017-0476-5
  • Primary Citation of Related Structures:  
    5YDZ, 5YE1, 5YE2, 5YE5

  • PubMed Abstract: 

    TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca 2+ 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 2+ , and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.


  • Organizational Affiliation

    Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mucolipin-1
A, B, C, D
580Mus musculusMutation(s): 0 
Gene Names: Mcoln1
Membrane Entity: Yes 
UniProt
Find proteins for Q99J21 (Mus musculus)
Explore Q99J21 
Go to UniProtKB:  Q99J21
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99J21
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION2.0

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-27
    Type: Initial release
  • Version 1.1: 2024-03-27
    Changes: Data collection, Database references