6wcb
From Proteopedia
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==Human open state TMEM175 in CsCl== | ==Human open state TMEM175 in CsCl== | ||
| - | <StructureSection load='6wcb' size='340' side='right'caption='[[6wcb]]' scene=''> | + | <StructureSection load='6wcb' size='340' side='right'caption='[[6wcb]], [[Resolution|resolution]] 3.17Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WCB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wcb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WCB FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wcb OCA], [http://pdbe.org/6wcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wcb RCSB], [http://www.ebi.ac.uk/pdbsum/6wcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wcb ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CS:CESIUM+ION'>CS</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TMEM175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wcb OCA], [http://pdbe.org/6wcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wcb RCSB], [http://www.ebi.ac.uk/pdbsum/6wcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wcb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/TM175_HUMAN TM175_HUMAN]] Disease susceptibility may be associated with variations affecting the gene represented in this entry. TMEM175 defects result in unstable lysosomal pH, leading to decreased lysosomal catalytic activity, decreased glucocerebrosidase activity, impaired autophagosome clearance by the lysosome and decreased mitochondrial respiration (PubMed:28193887).<ref>PMID:28193887</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/TM175_HUMAN TM175_HUMAN]] Organelle-specific potassium channel specifically responsible for potassium conductance in endosomes and lysosomes. Forms a potassium-permeable leak-like channel, which regulates lumenal pH stability and is required for autophagosome-lysosome fusion. Constitutes the major lysosomal potassium channel.<ref>PMID:26317472</ref> <ref>PMID:28723891</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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 A. 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. | ||
| + | |||
| + | Gating and selectivity mechanisms for the lysosomal K(+) channel TMEM175.,Oh S, Paknejad N, Hite RK Elife. 2020 Mar 31;9. pii: 53430. doi: 10.7554/eLife.53430. PMID:32228865<ref>PMID:32228865</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wcb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Hite | + | [[Category: Hite, R K]] |
| - | [[Category: Oh S]] | + | [[Category: Oh, S]] |
| - | [[Category: Paknejad N]] | + | [[Category: Paknejad, N]] |
| + | [[Category: Ion channel]] | ||
| + | [[Category: Lysosome]] | ||
| + | [[Category: Potassium channel]] | ||
| + | [[Category: Transport protein]] | ||
Revision as of 06:39, 7 October 2020
Human open state TMEM175 in CsCl
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