7unf
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==CryoEM structure of a mEAK7 bound human V-ATPase complex== |
| - | <StructureSection load='7unf' size='340' side='right'caption='[[7unf]]' scene=''> | + | <StructureSection load='7unf' size='340' side='right'caption='[[7unf]], [[Resolution|resolution]] 4.08Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7unf]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UNF FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7unf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7unf OCA], [https://pdbe.org/7unf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7unf RCSB], [https://www.ebi.ac.uk/pdbsum/7unf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7unf ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.08Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7unf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7unf OCA], [https://pdbe.org/7unf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7unf RCSB], [https://www.ebi.ac.uk/pdbsum/7unf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7unf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/VPP4_HUMAN VPP4_HUMAN] Autosomal recessive distal renal tubular acidosis. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/VPP4_HUMAN VPP4_HUMAN] Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Involved in normal vectorial acid transport into the urine by the kidney (PubMed:10973252, PubMed:12414817).[UniProtKB:Q29466][UniProtKB:Q93050]<ref>PMID:10973252</ref> <ref>PMID:12414817</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V(1) and V(o) domains in response to growth factor stimulation, nutrient sensing, and cellular differentiation. The molecular basis of its regulation by an endogenous modulator without affecting V-ATPase assembly remains unclear. Here, we discover that a lysosome-anchored protein termed (mammalian Enhancer-of-Akt-1-7 (mEAK7)) binds to intact V-ATPase. We determine cryo-EM structure of human mEAK7 in complex with human V-ATPase in native lipid-containing nanodiscs. The structure reveals that the TLDc domain of mEAK7 engages with subunits A, B, and E, while its C-terminal domain binds to subunit D, presumably blocking V(1)-V(o) torque transmission. Our functional studies suggest that mEAK7, which may act as a V-ATPase inhibitor, does not affect the activity of V-ATPase in vitro. However, overexpression of mEAK7 in HCT116 cells that stably express subunit a4 of V-ATPase represses the phosphorylation of ribosomal protein S6. Thus, this finding suggests that mEAK7 potentially links mTOR signaling with V-ATPase activity. | ||
| + | |||
| + | Molecular basis of mEAK7-mediated human V-ATPase regulation.,Wang R, Qin Y, Xie XS, Li X Nat Commun. 2022 Jun 7;13(1):3272. doi: 10.1038/s41467-022-30899-z. PMID:35672408<ref>PMID:35672408</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7unf" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[ATPase 3D structures|ATPase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Li X]] |
| + | [[Category: Wang R]] | ||
Current revision
CryoEM structure of a mEAK7 bound human V-ATPase complex
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