6WC9

Human open state TMEM175 in KCl


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.64 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Gating and selectivity mechanisms for the lysosomal K + channel TMEM175.

Oh, S.Paknejad, N.Hite, R.K.

(2020) Elife 9

  • DOI: https://doi.org/10.7554/eLife.53430
  • Primary Citation of Related Structures:  
    6WC9, 6WCA, 6WCB, 6WCC

  • PubMed Abstract: 

    Transmembrane protein 175 (TMEM175) is a K + -selective ion channel expressed in lysosomal membranes, where it establishes a membrane potential essential for lysosomal function and its dysregulation is associated with the development of Parkinson's Disease. TMEM175 is evolutionarily distinct from all known channels, predicting novel ion-selectivity and gating mechanisms. Here we present cryo-EM structures of human TMEM175 in open and closed conformations, enabled by resolutions up to 2.6 Å. Human TMEM175 adopts a homodimeric architecture with a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, these same residues establish a constriction essential for K + selectivity. These studies reveal the mechanisms of permeation, selectivity and gating and lay the groundwork for understanding the role of TMEM175 in lysosomal function.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endosomal/lysosomal potassium channel TMEM175
A, B
504Homo sapiensMutation(s): 0 
Gene Names: TMEM175
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BSA9 (Homo sapiens)
Explore Q9BSA9 
Go to UniProtKB:  Q9BSA9
PHAROS:  Q9BSA9
GTEx:  ENSG00000127419 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BSA9
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.64 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIXdev-3751
RECONSTRUCTIONcryoSPARC2.12

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesP30 CA008748

Revision History  (Full details and data files)

  • Version 1.0: 2020-04-15
    Type: Initial release
  • Version 1.1: 2020-10-07
    Changes: Database references, Derived calculations
  • Version 1.2: 2024-03-06
    Changes: Data collection, Database references