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Open data
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Basic information
Entry | Database: PDB / ID: 6wcc | ||||||
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Title | Human closed state TMEM175 in CsCl | ||||||
![]() | Endosomal/lysosomal potassium channel TMEM175 | ||||||
![]() | TRANSPORT PROTEIN / Ion Channel / Lysosome / Potassium Channel | ||||||
Function / homology | ![]() lysosomal lumen pH elevation / phagosome-lysosome fusion / regulation of lysosomal lumen pH / potassium ion leak channel activity / proton channel activity / arachidonate 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 / potassium ion leak channel activity / proton channel activity / arachidonate 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: 3.24 Å | ||||||
![]() | Oh, S. / Paknejad, N. / Hite, R.K. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Gating and selectivity mechanisms for the lysosomal K channel TMEM175. Authors: SeCheol Oh / Navid Paknejad / Richard K Hite / ![]() 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 ...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. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 248.4 KB | Display | ![]() |
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PDB format | ![]() | 201.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 21606MC ![]() 6wc9C ![]() 6wcaC ![]() 6wcbC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 55667.219 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Chemical | ChemComp-CS / #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human closed state TMEM175 in CsCl / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Dimeric channels | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K / Details: Blot for 4 seconds prior to plunging |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Image recording | Average exposure time: 8 sec. / Electron dose: 61 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 2 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4275219 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 70132 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL / Target criteria: FSC |