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| | <StructureSection load='7ped' size='340' side='right'caption='[[7ped]], [[Resolution|resolution]] 1.93Å' scene=''> | | <StructureSection load='7ped' size='340' side='right'caption='[[7ped]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7ped]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PED FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ped]] is a 2 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=7PED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PED FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DEPTOR, DEPDC6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</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=7ped FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ped OCA], [https://pdbe.org/7ped PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ped RCSB], [https://www.ebi.ac.uk/pdbsum/7ped PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ped ProSAT]</span></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=7ped FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ped OCA], [https://pdbe.org/7ped PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ped RCSB], [https://www.ebi.ac.uk/pdbsum/7ped PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ped ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DPTOR_HUMAN DPTOR_HUMAN]] Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes.<ref>PMID:19446321</ref>
| + | [https://www.uniprot.org/uniprot/DPTOR_HUMAN DPTOR_HUMAN] Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes.<ref>PMID:19446321</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jakob, R]] | + | [[Category: Jakob R]] |
| - | [[Category: Maier, T]] | + | [[Category: Maier T]] |
| - | [[Category: Waelchli, M]] | + | [[Category: Waelchli M]] |
| - | [[Category: Dep-domain]]
| + | |
| - | [[Category: Deptor]]
| + | |
| - | [[Category: Mtor]]
| + | |
| - | [[Category: Mtor-binding]]
| + | |
| - | [[Category: Mtorc1]]
| + | |
| - | [[Category: Mtorc2]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
DPTOR_HUMAN Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes.[1]
Publication Abstract from PubMed
The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as an anchor for DEPt association that allosterically suppresses mTOR activation. The binding interfaces of the PDZ domain and DEPt also support further regulation by other signaling pathways. A separate, substrate-like mode of interaction for DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted interplay between DEPTOR and mTOR provides a basis for understanding the divergent roles of DEPTOR in physiology and opens new routes for targeting the mTOR-DEPTOR interaction in disease.
Regulation of human mTOR complexes by DEPTOR.,Walchli M, Berneiser K, Mangia F, Imseng S, Craigie LM, Stuttfeld E, Hall MN, Maier T Elife. 2021 Sep 14;10. pii: 70871. doi: 10.7554/eLife.70871. PMID:34519268[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009 May 29;137(5):873-86. doi: 10.1016/j.cell.2009.03.046. Epub 2009 May, 14. PMID:19446321 doi:http://dx.doi.org/10.1016/j.cell.2009.03.046
- ↑ Walchli M, Berneiser K, Mangia F, Imseng S, Craigie LM, Stuttfeld E, Hall MN, Maier T. Regulation of human mTOR complexes by DEPTOR. Elife. 2021 Sep 14;10. pii: 70871. doi: 10.7554/eLife.70871. PMID:34519268 doi:http://dx.doi.org/10.7554/eLife.70871
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