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| <StructureSection load='3t5g' size='340' side='right'caption='[[3t5g]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='3t5g' size='340' side='right'caption='[[3t5g]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3t5g]] 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=3T5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T5G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t5g]] 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=3T5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T5G FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAR:FARNESYL'>FAR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 1.7Å</td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=FAR:FARNESYL'>FAR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t5i|3t5i]]</div></td></tr>
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- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RHEB, RHEB2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDE6D, PDED ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3t5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5g OCA], [https://pdbe.org/3t5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t5g RCSB], [https://www.ebi.ac.uk/pdbsum/3t5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5g 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=3t5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5g OCA], [https://pdbe.org/3t5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t5g RCSB], [https://www.ebi.ac.uk/pdbsum/3t5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5g ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/RHEB_HUMAN RHEB_HUMAN]] Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Activates the protein kinase activity of mTORC1. Has low intrinsic GTPase activity.<ref>PMID:12271141</ref> <ref>PMID:12869586</ref> <ref>PMID:15340059</ref> <ref>PMID:15854902</ref> <ref>PMID:16098514</ref> <ref>PMID:20381137</ref> [[https://www.uniprot.org/uniprot/PDE6D_HUMAN PDE6D_HUMAN]] Acts as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude and does so by decreasing the nucleotide dissociation rate. Stabilizes Arl3-GTP by decreasing the nucleotide dissociation (By similarity).
| + | [https://www.uniprot.org/uniprot/RHEB_HUMAN RHEB_HUMAN] Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Activates the protein kinase activity of mTORC1. Has low intrinsic GTPase activity.<ref>PMID:12271141</ref> <ref>PMID:12869586</ref> <ref>PMID:15340059</ref> <ref>PMID:15854902</ref> <ref>PMID:16098514</ref> <ref>PMID:20381137</ref> |
- | <div style="background-color:#fffaf0;">
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- | == Publication Abstract from PubMed ==
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- | Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEdelta is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEdelta. The structure explains the nucleotide-independent binding of Rheb to PDEdelta and the relaxed specificity of PDEdelta. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEdelta for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy.
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- | | + | |
- | Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo.,Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A Nat Chem Biol. 2011 Oct 16. doi: 10.1038/nchembio.686. PMID:22002721<ref>PMID:22002721</ref>
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- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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- | </div>
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- | <div class="pdbe-citations 3t5g" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Chen, Y X]] | + | [[Category: Chen Y-X]] |
- | [[Category: Ismail, S A]] | + | [[Category: Ismail SA]] |
- | [[Category: Wittinghofer, A]] | + | [[Category: Wittinghofer A]] |
- | [[Category: Farnesyl]]
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- | [[Category: Immunoglobulin-like beta sandwitch]]
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- | [[Category: Lipid binding protein]]
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- | [[Category: Pde delta]]
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- | [[Category: Rheb]]
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- | [[Category: Signaling protein]]
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