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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21604 | |||||||||
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Title | Human closed state TMEM175 in KCl | |||||||||
![]() | Human closed state TMEM175 in KCl | |||||||||
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![]() | Ion Channel / Lysosome / Potassium Channel / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() lysosomal lumen pH elevation / phagosome-lysosome fusion / arachidonate binding / regulation of lysosomal lumen pH / potassium ion leak channel activity / proton channel activity / potassium channel activity / potassium ion transmembrane transport / proton transmembrane transport / neuron cellular homeostasis ...lysosomal lumen pH elevation / phagosome-lysosome fusion / arachidonate binding / regulation of lysosomal lumen pH / potassium ion leak channel activity / proton channel activity / potassium channel activity / potassium ion transmembrane transport / proton transmembrane transport / neuron cellular homeostasis / endosome / endosome membrane / lysosome / lysosomal membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.03 Å | |||||||||
![]() | Oh S / Paknejad N | |||||||||
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 | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.5 KB 14.5 KB | Display Display | ![]() |
Images | ![]() | 72.1 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 457.4 KB | Display | ![]() |
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Full document | ![]() | 457 KB | Display | |
Data in XML | ![]() | 4.5 KB | Display | |
Data in CIF | ![]() | 5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wcaMC ![]() 6wc9C ![]() 6wcbC ![]() 6wccC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Human closed state TMEM175 in KCl | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.088 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Human closed state TMEM175 in KCl
Entire | Name: Human closed state TMEM175 in KCl |
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Components |
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-Supramolecule #1: Human closed state TMEM175 in KCl
Supramolecule | Name: Human closed state TMEM175 in KCl / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Endosomal/lysosomal potassium channel TMEM175
Macromolecule | Name: Endosomal/lysosomal potassium channel TMEM175 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 55.667219 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSQPRTPEQA LDTPGDCPPG RRDEDAGEGI QCSQRMLSFS DALLSIIATV MILPVTHTEI SPEQQFDRSV QRLLATRIAV YLMTFLIVT VAWAAHTRLF QVVGKTDDTL ALLNLACMMT ITFLPYTFSL MVTFPDVPLG IFLFCVCVIA IGVVQALIVG Y AFHFPHLL ...String: MSQPRTPEQA LDTPGDCPPG RRDEDAGEGI QCSQRMLSFS DALLSIIATV MILPVTHTEI SPEQQFDRSV QRLLATRIAV YLMTFLIVT VAWAAHTRLF QVVGKTDDTL ALLNLACMMT ITFLPYTFSL MVTFPDVPLG IFLFCVCVIA IGVVQALIVG Y AFHFPHLL SPQIQRSAHR ALYRRHVLGI VLQGPALCFA AAIFSLFFVP LSYLLMVTVI LLPYVSKVTG WCRDRLLGHR EP SAHPVEV FSFDLHEPLS KERVEAFSDG VYAIVATLLI LDICEDNVPD PKDVKERFSG SLVAALSATG PRFLAYFGSF ATV GLLWFA HHSLFLHVRK ATRAMGLLNT LSLAFVGGLP LAYQQTSAFA RQPRDELERV RVSCTIIFLA SIFQLAMWTT ALLH QAETL QPSVWFGGRE HVLMFAKLAL YPCASLLAFA STCLLSRFSV GIFHLMQIAV PCAFLLLRLL VGLALATLRV LRGLA RPEH PPPAPTGQDD PQSQLLPAPC UniProtKB: Endosomal/lysosomal proton channel TMEM175 |
-Macromolecule #2: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 2 / Number of copies: 5 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Macromolecule #3: water
Macromolecule | Name: water / type: ligand / ID: 3 / Number of copies: 26 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5 mg/mL | |||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 10 sec. | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 4 seconds prior to plunging. | |||||||||||||||
Details | Dimeric channels |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-40 / Number grids imaged: 2 / Average exposure time: 8.0 sec. / Average electron dose: 61.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER / Target criteria: FSC |
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Output model | ![]() PDB-6wca: |