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| | ==NMR structure of the oxidized yeast TOR1 FATC domain bound to DPC micelles at 318K== | | ==NMR structure of the oxidized yeast TOR1 FATC domain bound to DPC micelles at 318K== |
| - | <StructureSection load='2kio' size='340' side='right' caption='[[2kio]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kio' size='340' side='right'caption='[[2kio]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kio]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KIO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kio]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIO FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w1n|1w1n]], [[2kit|2kit]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DRR1, J1803, TOR1, YJR066W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</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=2kio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kio OCA], [https://pdbe.org/2kio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kio RCSB], [https://www.ebi.ac.uk/pdbsum/2kio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kio ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=2kio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kio OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kio RCSB], [http://www.ebi.ac.uk/pdbsum/2kio PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOR1_YEAST TOR1_YEAST]] Phosphatidylinositol 3-kinase homolog, component of TORC1, which regulates multiple cellular processes to control cell growth in response to environmental signals. Nutrient limitation and environmental stress signals cause inactivation of TORC1. Active TORC1 positively controls ribosome biogenesis via control of rRNA, ribosomal protein and tRNA gene expression, and rRNA processing. TORC1 positively controls protein biosynthesis by regulation of mRNA stability, translation initiation factor activity, and high-affinity amino acid permeases that serve to provide amino acids for use by the translation machinery. TORC1 also promotes growth by sequestering a number of nutrient and general stress-responsive transcription factors in the cytoplasm. TORC1 negatively controls macroautophagy, a process to recycle surplus cytoplasmic mass under nutrient starvation conditions. TORC1 controls many of these processes via TIP41-TAP42-mediated inhibition of the type 2A-related phosphatases PP2A and SIT4.<ref>PMID:7606777</ref> <ref>PMID:8741837</ref> <ref>PMID:9843498</ref> <ref>PMID:9539725</ref> <ref>PMID:10329624</ref> <ref>PMID:10198052</ref> <ref>PMID:10604478</ref> <ref>PMID:10995454</ref> <ref>PMID:11741537</ref> <ref>PMID:15620355</ref> | + | [https://www.uniprot.org/uniprot/TOR1_YEAST TOR1_YEAST] Phosphatidylinositol 3-kinase homolog, component of TORC1, which regulates multiple cellular processes to control cell growth in response to environmental signals. Nutrient limitation and environmental stress signals cause inactivation of TORC1. Active TORC1 positively controls ribosome biogenesis via control of rRNA, ribosomal protein and tRNA gene expression, and rRNA processing. TORC1 positively controls protein biosynthesis by regulation of mRNA stability, translation initiation factor activity, and high-affinity amino acid permeases that serve to provide amino acids for use by the translation machinery. TORC1 also promotes growth by sequestering a number of nutrient and general stress-responsive transcription factors in the cytoplasm. TORC1 negatively controls macroautophagy, a process to recycle surplus cytoplasmic mass under nutrient starvation conditions. TORC1 controls many of these processes via TIP41-TAP42-mediated inhibition of the type 2A-related phosphatases PP2A and SIT4.<ref>PMID:7606777</ref> <ref>PMID:8741837</ref> <ref>PMID:9843498</ref> <ref>PMID:9539725</ref> <ref>PMID:10329624</ref> <ref>PMID:10198052</ref> <ref>PMID:10604478</ref> <ref>PMID:10995454</ref> <ref>PMID:11741537</ref> <ref>PMID:15620355</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kio_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kio_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kio ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2kio" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Dames, S A]] | + | [[Category: Dames SA]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Dpc micelle]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Membrane-mimetic]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Vacuole]]
| + | |
| Structural highlights
Function
TOR1_YEAST Phosphatidylinositol 3-kinase homolog, component of TORC1, which regulates multiple cellular processes to control cell growth in response to environmental signals. Nutrient limitation and environmental stress signals cause inactivation of TORC1. Active TORC1 positively controls ribosome biogenesis via control of rRNA, ribosomal protein and tRNA gene expression, and rRNA processing. TORC1 positively controls protein biosynthesis by regulation of mRNA stability, translation initiation factor activity, and high-affinity amino acid permeases that serve to provide amino acids for use by the translation machinery. TORC1 also promotes growth by sequestering a number of nutrient and general stress-responsive transcription factors in the cytoplasm. TORC1 negatively controls macroautophagy, a process to recycle surplus cytoplasmic mass under nutrient starvation conditions. TORC1 controls many of these processes via TIP41-TAP42-mediated inhibition of the type 2A-related phosphatases PP2A and SIT4.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
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
The target of rapamycin (TOR) is a conserved eukaryotic Ser/Thr kinase that regulates cellular growth in response to the nutrient and energy state. TOR signaling plays an important role in the development of diseases such as cancer, obesity, and diabetes and in different redox-sensitive processes (hypoxia, apoptosis, and aging). Because TOR has been detected at different cellular membranes and in the nucleus, its localization may influence the specific signaling readout. To better understand how TOR can associate with different membranes, the lipid-binding properties of the redox-sensitive yeast TOR1 FATC domain (y1fatc) have been characterized by solution NMR spectroscopy. Binding studies with different lipids indicate that y1fatc interacts specifically with a membrane-mimetic environment but appears not to recognize a specific lipid headgroup. In both, the structures of oxidized and reduced micelle-bound y1fatc, residues Ile-2456 to Trp-2470 of the lipid-binding motif form a hydrophobic bulb that has a rim of charged residues. The diffusion constants for both micelle-bound states are consistent with the rotational correlation times from the analysis of the (15)N relaxation data. Based on the K(d) values, the oxidized form (K(d) approximately 0.31 mm) binds dodecyl phosphocholine micelles slightly tighter than the reduced form (K(d) approximately 1.86 mM). Binding studies with y1fatc in which one or both tryptophans (Trp-2466 and Trp-2470) were replaced by alanine suggest that these residues are important for the exact positioning in the membrane and that the other aromatic (His-2462, Tyr-2463, and Phe-2469) and aliphatic residues (Ile-2456, Leu-2459, Ile-2464, and Pro-2468) in the lipid-binding motif contribute significantly to the affinity.
Structural basis for the association of the redox-sensitive target of rapamycin FATC domain with membrane-mimetic micelles.,Dames SA J Biol Chem. 2010 Mar 5;285(10):7766-75. Epub 2009 Dec 30. PMID:20042596[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zheng XF, Florentino D, Chen J, Crabtree GR, Schreiber SL. TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin. Cell. 1995 Jul 14;82(1):121-30. PMID:7606777
- ↑ Barbet NC, Schneider U, Helliwell SB, Stansfield I, Tuite MF, Hall MN. TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell. 1996 Jan;7(1):25-42. PMID:8741837
- ↑ Schmidt A, Beck T, Koller A, Kunz J, Hall MN. The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J. 1998 Dec 1;17(23):6924-31. PMID:9843498 doi:http://dx.doi.org/10.1093/emboj/17.23.6924
- ↑ Berset C, Trachsel H, Altmann M. The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4264-9. PMID:9539725
- ↑ Jiang Y, Broach JR. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J. 1999 May 17;18(10):2782-92. PMID:10329624 doi:http://dx.doi.org/10.1093/emboj/18.10.2782
- ↑ Powers T, Walter P. Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol Biol Cell. 1999 Apr;10(4):987-1000. PMID:10198052
- ↑ Beck T, Hall MN. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature. 1999 Dec 9;402(6762):689-92. PMID:10604478 doi:http://dx.doi.org/10.1038/45287
- ↑ Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol. 2000 Sep 18;150(6):1507-13. PMID:10995454
- ↑ Jacinto E, Guo B, Arndt KT, Schmelzle T, Hall MN. TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway. Mol Cell. 2001 Nov;8(5):1017-26. PMID:11741537
- ↑ Martin DE, Soulard A, Hall MN. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell. 2004 Dec 29;119(7):969-79. PMID:15620355 doi:http://dx.doi.org/S0092867404011511
- ↑ Dames SA. Structural basis for the association of the redox-sensitive target of rapamycin FATC domain with membrane-mimetic micelles. J Biol Chem. 2010 Mar 5;285(10):7766-75. Epub 2009 Dec 30. PMID:20042596 doi:10.1074/jbc.M109.058404
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