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| | ==Solution structure of the 21 kDa GTPase RHEB bound to GDP== | | ==Solution structure of the 21 kDa GTPase RHEB bound to GDP== |
| - | <StructureSection load='2l0x' size='340' side='right' caption='[[2l0x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l0x' size='340' side='right'caption='[[2l0x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l0x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L0X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L0X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l0x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L0X 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='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=10116 Buffalo rat])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rheb ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=2l0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l0x OCA], [http://pdbe.org/2l0x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l0x RCSB], [http://www.ebi.ac.uk/pdbsum/2l0x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l0x 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=2l0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l0x OCA], [https://pdbe.org/2l0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l0x RCSB], [https://www.ebi.ac.uk/pdbsum/2l0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l0x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RHEB_RAT RHEB_RAT]] 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_RAT RHEB_RAT]] 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). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Buffalo rat]] | | [[Category: Buffalo rat]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Berghaus, C]] | | [[Category: Berghaus, C]] |
| | [[Category: Heumann, R]] | | [[Category: Heumann, R]] |
| Structural highlights
Function
[RHEB_RAT] 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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Rheb is a homolog of Ras GTPase that regulates cell growth, proliferation, and regeneration via mammalian target of rapamycin (mTOR). Due to the well established potential of activated Ras to promote survival, we sought to investigate the ability of Rheb signaling to phenocopy Ras. We found that over-expression of lipid-anchored Rheb enhanced the apoptotic effects induced by UV light, tumor necrosis factor alpha (TNFalpha), or tunicamycin in an mTOR complex 1 (mTORC1)-dependent manner. Knocking down endogenous Rheb or applying rapamycin led to partial protection, identifying Rheb as a mediator of cell death. Ras and cRaf kinase opposed the apoptotic effects induced by UV light or TNFalpha but did not prevent Rheb-mediated apoptosis. In order to gain structural insight into the signaling mechanisms, we determined the structure of Rheb-GDP by nuclear magnetic resonance (NMR). The complex adopts the typical canonical fold of RasGTPases and displays the characteristic GDP-dependent picosecond to nanosecond backbone dynamics of the switch-I and switch-II regions. NMR revealed Ras effector-like binding of activated Rheb to cRaf-Ras-binding-domain (RBD), but the affinity was 1000-fold lower than the Ras/RBD interaction, suggesting a lack of functional interaction. ShRNA-mediated knockdown of apoptosis signaling kinase-1 (ASK-1) strongly reduced UV or TNFalpha-induced apoptosis and suppressed enhancement by Rheb over-expression. In conclusion, Rheb-mTOR activation not only promotes normal cell growth but also enhances apoptosis in response to diverse toxic stimuli via an ASK-1-mediated mechanism. Pharmacological regulation of the Rheb/mTORC1 pathway using rapamycin should take the presence of cellular stress into consideration, which may have clinical implications.
Ras homolog enriched in brain (Rheb) enhances apoptotic signaling.,Karassek S, Berghaus C, Schwarten M, Goemans CG, Ohse N, Kock G, Jockers K, Neumann S, Gottfried S, Herrmann C, Heumann R, Stoll R J Biol Chem. 2010 Aug 4. PMID:20685651[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Karassek S, Berghaus C, Schwarten M, Goemans CG, Ohse N, Kock G, Jockers K, Neumann S, Gottfried S, Herrmann C, Heumann R, Stoll R. Ras homolog enriched in brain (Rheb) enhances apoptotic signaling. J Biol Chem. 2010 Aug 4. PMID:20685651 doi:10.1074/jbc.M109.095968
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