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| | ==Structure of Mus musculus Rheb G63V mutant bound to GDP== | | ==Structure of Mus musculus Rheb G63V mutant bound to GDP== |
| - | <StructureSection load='4o2r' size='340' side='right' caption='[[4o2r]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4o2r' size='340' side='right'caption='[[4o2r]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o2r]] 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=4O2R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O2R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o2r]] 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=4O2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O2R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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">[[4o25|4o25]], [[4o2l|4o2l]]</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=4o2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o2r OCA], [https://pdbe.org/4o2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o2r RCSB], [https://www.ebi.ac.uk/pdbsum/4o2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o2r ProSAT]</span></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>
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| - | <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=4o2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o2r OCA], [http://pdbe.org/4o2r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o2r RCSB], [http://www.ebi.ac.uk/pdbsum/4o2r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o2r 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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 == | | == References == |
| | <references/> | | <references/> |
| | __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: Gdp]]
| + | [[Category: Stambolic V]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Small gtpase]]
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| Structural highlights
Function
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).
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mazhab-Jafari MT, Marshall CB, Ho J, Ishiyama N, Stambolic V, Ikura M. Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR). J Biol Chem. 2014 May 2;289(18):12195-201. doi: 10.1074/jbc.C113.543736. Epub, 2014 Mar 19. PMID:24648513 doi:http://dx.doi.org/10.1074/jbc.C113.543736
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