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| | ==Structure of Wild Type Mus musculus Rheb bound to GTP== | | ==Structure of Wild Type Mus musculus Rheb bound to GTP== |
| - | <StructureSection load='4o25' size='340' side='right' caption='[[4o25]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4o25' size='340' side='right'caption='[[4o25]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o25]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O25 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o25]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O25 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o2l|4o2l]], [[4o2r|4o2r]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rheb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4o25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o25 OCA], [https://pdbe.org/4o25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o25 RCSB], [https://www.ebi.ac.uk/pdbsum/4o25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o25 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o25 OCA], [http://pdbe.org/4o25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o25 RCSB], [http://www.ebi.ac.uk/pdbsum/4o25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o25 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RHEB_MOUSE RHEB_MOUSE]] Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Activates the protein kinase activity of mTORC1. Has low intrinsic GTPase activity (By similarity). | + | [https://www.uniprot.org/uniprot/RHEB_MOUSE RHEB_MOUSE] Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Activates the protein kinase activity of mTORC1. Has low intrinsic GTPase activity (By similarity). |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Constitutively activated variants of small GTPases, which provide valuable functional probes of their role in cellular signaling pathways, can often be generated by mutating the canonical catalytic residue (e.g. Ras Q61L) to impair GTP hydrolysis. However, this general approach is ineffective for a substantial fraction of the small GTPase family in which this residue is not conserved (e.g. Rap) or not catalytic (e.g. Rheb). Using a novel engineering approach, we have manipulated nucleotide binding through structure-guided substitutions of an ultraconserved glycine residue in the G3-box motif (DXXG). Substitution of Rheb Gly-63 with alanine impaired both intrinsic and TSC2 GTPase-activating protein (GAP)-mediated GTP hydrolysis by displacing the hydrolytic water molecule, whereas introduction of a bulkier valine side chain selectively blocked GTP binding by steric occlusion of the gamma-phosphate. Rheb G63A stimulated phosphorylation of the mTORC1 substrate p70S6 kinase more strongly than wild-type, thus offering a new tool for mammalian target of rapamycin (mTOR) signaling.
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| - | Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR).,Mazhab-Jafari MT, Marshall CB, Ho J, Ishiyama N, Stambolic V, Ikura M J Biol Chem. 2014 May 2;289(18):12195-201. doi: 10.1074/jbc.C113.543736. Epub, 2014 Mar 19. PMID:24648513<ref>PMID:24648513</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 4o25" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[GTP-binding protein|GTP-binding protein]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Ho, J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ikura, M]] | + | [[Category: Ho J]] |
| - | [[Category: Ishiyama, N]] | + | [[Category: Ikura M]] |
| - | [[Category: Marshall, C B]] | + | [[Category: Ishiyama N]] |
| - | [[Category: Mazhab-Jafari, M T]] | + | [[Category: Marshall CB]] |
| - | [[Category: Stambolic, V]] | + | [[Category: Mazhab-Jafari MT]] |
| - | [[Category: Gtp and gdp]]
| + | [[Category: Stambolic V]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Small gtpase]]
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