+
Open data
-
Basic information
Entry | Database: PDB / ID: 7lf6 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of lysosomal membrane protein | ||||||
![]() | Endosomal/lysosomal potassium channel TMEM175 | ||||||
![]() | MEMBRANE PROTEIN / Channel | ||||||
Function / homology | ![]() lysosomal lumen pH elevation / phagosome-lysosome fusion / regulation of lysosomal lumen pH / proton channel activity / potassium ion leak channel activity / arachidonic acid binding / potassium channel activity / potassium ion transmembrane transport / proton transmembrane transport / neuron cellular homeostasis ...lysosomal lumen pH elevation / phagosome-lysosome fusion / regulation of lysosomal lumen pH / proton channel activity / potassium ion leak channel activity / arachidonic acid binding / potassium channel activity / potassium ion transmembrane transport / proton transmembrane transport / neuron cellular homeostasis / lysosome / endosome membrane / endosome / lysosomal membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Shen, C. / Fu, T.M. / Wang, L.F. / Rawson, S. / Wu, H. | ||||||
![]() | ![]() Title: pH regulates potassium conductance and drives a constitutive proton current in human TMEM175. Authors: Wang Zheng / Chen Shen / Longfei Wang / Shaun Rawson / Wen Jun Xie / Carl Nist-Lund / Jason Wu / Zhangfei Shen / Shiyu Xia / Jeffrey R Holt / Hao Wu / Tian-Min Fu / ![]() Abstract: Human TMEM175, a noncanonical potassium (K) channel in endolysosomes, contributes to their pH stability and is implicated in the pathogenesis of Parkinson's disease (PD). Structurally, the TMEM175 ...Human TMEM175, a noncanonical potassium (K) channel in endolysosomes, contributes to their pH stability and is implicated in the pathogenesis of Parkinson's disease (PD). Structurally, the TMEM175 family exhibits an architecture distinct from canonical potassium channels, as it lacks the typical TVGYG selectivity filter. Here, we show that human TMEM175 not only exhibits pH-dependent structural changes that reduce K permeation at acidic pH but also displays proton permeation. TMEM175 constitutively conducts K at pH 7.4 but displays reduced K permeation at lower pH. In contrast, proton current through TMEM175 increases with decreasing pH because of the increased proton gradient. Molecular dynamics simulation, structure-based mutagenesis, and electrophysiological analysis suggest that K ions and protons share the same permeation pathway. The M393T variant of human TMEM175 associated with PD shows reduced function in both K and proton permeation. Together, our structural and electrophysiological analysis reveals a mechanism of TMEM175 regulation by pH. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 141.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 114.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 721.2 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 737.7 KB | Display | |
Data in XML | ![]() | 29.4 KB | Display | |
Data in CIF | ![]() | 43.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23300MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 55667.219 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Dimer of a membrane protein / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 5.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 66.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 117539 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|