7dkl: Difference between revisions

Latest revision as of 16:35, 29 November 2023

Crystal structure of the tandem DEP domains of DEPTOR

Structural highlights

7dkl is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPTOR_HUMAN Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes.^[1]

Publication Abstract from PubMed

DEP domain containing mTOR-interacting protein (DEPTOR) plays pivotal roles in regulating metabolism, growth, autophagy and apoptosis by functions as an endogenous inhibitor of mTOR signaling pathway. Activated by phosphatidic acid, a second messenger in mTOR signaling, DEPTOR dissociates from mTORC1 complex with unknown mechanism. Here, we present a 1.5 A resolution crystal structure, which shows that the N-terminal two tandem DEP domains of hDEPTOR fold into a dumbbell-shaped structure, protruding the characteristic beta-hairpin arms of DEP domains on each side. An 18 amino acids DDEX motif at the end of DEP2 interacts with DEP1 and stabilizes the structure. Biochemical studies showed that the tandem DEP domains directly interact with phosphatidic acid using two distinct positively charged patches. These results provide insights into mTOR activation upon phosphatidic acid stimulation.

Structural Basis of DEPTOR to Recognize Phosphatidic Acid Using its Tandem DEP Domains.,Weng Z, Shen X, Zheng J, Liang H, Liu Y J Mol Biol. 2021 Jun 25;433(13):166989. doi: 10.1016/j.jmb.2021.166989. Epub 2021, Apr 16. PMID:33865870^[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:https://dx.doi.org/10.1016/j.cell.2009.03.046
↑ Weng Z, Shen X, Zheng J, Liang H, Liu Y. Structural Basis of DEPTOR to Recognize Phosphatidic Acid Using its Tandem DEP Domains. J Mol Biol. 2021 Jun 25;433(13):166989. doi: 10.1016/j.jmb.2021.166989. Epub 2021, Apr 16. PMID:33865870 doi:https://dx.doi.org/10.1016/j.jmb.2021.166989

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1016/j.cell.2009.03.046

[2] Weng Z, Shen X, Zheng J, Liang H, Liu Y. Structural Basis of DEPTOR to Recognize Phosphatidic Acid Using its Tandem DEP Domains. J Mol Biol. 2021 Jun 25;433(13):166989. doi: 10.1016/j.jmb.2021.166989. Epub 2021, Apr 16. PMID:33865870 doi:https://dx.doi.org/10.1016/j.jmb.2021.166989

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='7dkl' size='340' side='right'caption='[[7dkl]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7dkl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DKL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7dkl]] is a 1 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=7DKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DKL 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=7dkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dkl OCA], [https://pdbe.org/7dkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dkl RCSB], [https://www.ebi.ac.uk/pdbsum/7dkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dkl ProSAT]</span></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]] 1.5&#8491;</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=7dkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dkl OCA], [https://pdbe.org/7dkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dkl RCSB], [https://www.ebi.ac.uk/pdbsum/7dkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dkl ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Liu, Y F]]
+[[Category: Liu YF]]
-[[Category: Shen, X X]]
+[[Category: Shen XX]]
-[[Category: Weng, Z F]]
+[[Category: Weng ZF]]
-[[Category: Anionic lipid binding protein]]
-[[Category: Dep domain]]
-[[Category: Lipid binding protein]]
-[[Category: Mtor inhibitor]]
-[[Category: Pa binding protein]]

7dkl: Difference between revisions

Latest revision as of 16:35, 29 November 2023

Crystal structure of the tandem DEP domains of DEPTOR

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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