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5ifs
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Quantitative interaction mapping reveals an extended ubiquitin regulatory domain in ASPL that disrupts functional p97 hexamers and induces cell death== | |
| + | <StructureSection load='5ifs' size='340' side='right'caption='[[5ifs]], [[Resolution|resolution]] 2.46Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ifs]] is a 4 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=5IFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IFS FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.46Å</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5ifs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ifs OCA], [https://pdbe.org/5ifs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ifs RCSB], [https://www.ebi.ac.uk/pdbsum/5ifs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ifs ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ASPC1_HUMAN ASPC1_HUMAN] Translocation renal cell carcinoma;Alveolar soft-tissue sarcoma. A chromosomal aberration involving ASPSCR1 is found in patients with alveolar soft part sarcoma. Translocation t(X;17)(p11;q25) with TFE3 forms a ASPSCR1-TFE3 fusion protein.<ref>PMID:11244503</ref> A chromosomal aberration involving ASPSCR1 has been found in two patients with of papillary renal cell carcinoma. Translocation t(X;17)(p11.2;q25).<ref>PMID:11358836</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ASPC1_HUMAN ASPC1_HUMAN] Tethering protein that sequesters GLUT4-containing vesicles in the cytoplasm in the absence of insulin. Modulates the amount of GLUT4 that is available at the cell surface (By similarity). Enhances VCP methylation catalyzed by VCPKMT.<ref>PMID:23349634</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report the generation of a quantitative interaction network, directly linking 14 human proteins to the AAA+ ATPase p97, an essential hexameric protein with multiple cellular functions. We show that the high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers. High-resolution structural and biochemical studies indicate that an extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers. This spontaneous process is accompanied by a reorientation of the D2 ATPase domain in p97 and a loss of its activity. Finally, we demonstrate that overproduction of ASPL disrupts p97 hexamer function in ERAD and that engineered eUBX polypeptides can induce cell death, providing a rationale for developing anti-cancer polypeptide inhibitors that may target p97 activity. | ||
| - | + | Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers.,Arumughan A, Roske Y, Barth C, Forero LL, Bravo-Rodriguez K, Redel A, Kostova S, McShane E, Opitz R, Faelber K, Rau K, Mielke T, Daumke O, Selbach M, Sanchez-Garcia E, Rocks O, Panakova D, Heinemann U, Wanker EE Nat Commun. 2016 Oct 20;7:13047. doi: 10.1038/ncomms13047. PMID:27762274<ref>PMID:27762274</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5ifs" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[ATPase 3D structures|ATPase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Arumughan A]] | ||
| + | [[Category: Heinemann U]] | ||
| + | [[Category: Roske Y]] | ||
| + | [[Category: Wanker E]] | ||
Current revision
Quantitative interaction mapping reveals an extended ubiquitin regulatory domain in ASPL that disrupts functional p97 hexamers and induces cell death
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