1w1n

From Proteopedia

(Difference between revisions)

Revision as of 08:16, 10 November 2021

The solution structure of the FATC Domain of the Protein Kinase TOR1 from yeast

Structural highlights

1w1n is a 1 chain structure with sequence from Atcc 18824. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Phosphatidylinositol 3-kinase, with EC number 2.7.1.137
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 highly conserved Ser/Thr kinase that plays a central role in the control of cellular growth. TOR has a characteristic multidomain structure. Only the kinase domain has catalytic function; the other domains are assumed to mediate interactions with TOR substrates and regulators. Except for the rapamycin-binding domain, there are no high-resolution structural data available for TOR. Here, we present a structural, biophysical, and mutagenesis study of the extremely conserved COOH-terminal FATC domain. The importance of this domain for TOR function has been highlighted in several publications. We show that the FATC domain, in its oxidized form, exhibits a novel structural motif consisting of an alpha-helix and a COOH-terminal disulfide-bonded loop between two completely conserved cysteine residues. Upon reduction, the flexibility of the loop region increases dramatically. The structural data, the redox potential of the disulfide bridge, and the biochemical data of a cysteine to serine mutant indicate that the intracellular redox potential can affect the cellular amount of the TOR protein via the FATC domain. Because the amount of TOR mRNA is not changed, the redox state of the FATC disulfide bond is probably influencing the degradation of TOR.

The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability.,Dames SA, Mulet JM, Rathgeb-Szabo K, Hall MN, Grzesiek S J Biol Chem. 2005 May 27;280(21):20558-64. Epub 2005 Mar 16. PMID:15772072^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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, Mulet JM, Rathgeb-Szabo K, Hall MN, Grzesiek S. The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. J Biol Chem. 2005 May 27;280(21):20558-64. Epub 2005 Mar 16. PMID:15772072 doi:10.1074/jbc.M501116200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w1n"

@@ Line 3: / Line 3: @@
 <StructureSection load='1w1n' size='340' side='right'caption='[[1w1n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1w1n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W1N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W1N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1w1n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W1N FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></td></tr>
+</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </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=1w1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w1n OCA], [http://pdbe.org/1w1n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w1n RCSB], [http://www.ebi.ac.uk/pdbsum/1w1n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w1n 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=1w1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w1n OCA], [https://pdbe.org/1w1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w1n RCSB], [https://www.ebi.ac.uk/pdbsum/1w1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w1n ProSAT]</span></td></tr>
 </table>
 == 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 ==
 [[Image:Consurf_key_small.gif|200px|right]]

1w1n

From Proteopedia

Revision as of 08:16, 10 November 2021

The solution structure of the FATC Domain of the Protein Kinase TOR1 from yeast

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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