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| | ==Crystal Structure of TSC1 core domain from S. pombe== | | ==Crystal Structure of TSC1 core domain from S. pombe== |
| - | <StructureSection load='4kk0' size='340' side='right' caption='[[4kk0]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4kk0' size='340' side='right'caption='[[4kk0]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kk0]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KK0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kk0]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KK0 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kk1|4kk1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPAC22F3.13, tsc1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Schizosaccharomyces pombe 972h-])</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=4kk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kk0 OCA], [https://pdbe.org/4kk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kk0 RCSB], [https://www.ebi.ac.uk/pdbsum/4kk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kk0 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=4kk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kk0 RCSB], [http://www.ebi.ac.uk/pdbsum/4kk0 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TSC1_SCHPO TSC1_SCHPO]] Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.<ref>PMID:12136010</ref> <ref>PMID:14718525</ref> <ref>PMID:16624901</ref> | + | [https://www.uniprot.org/uniprot/TSC1_SCHPO TSC1_SCHPO] Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.<ref>PMID:12136010</ref> <ref>PMID:14718525</ref> <ref>PMID:16624901</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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 4kk0" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Schizosaccharomyces pombe 972h-]] | | [[Category: Schizosaccharomyces pombe 972h-]] |
| - | [[Category: Gao, F]] | + | [[Category: Gao F]] |
| - | [[Category: Gong, W M]] | + | [[Category: Gong WM]] |
| - | [[Category: Lou, J Z]] | + | [[Category: Lou JZ]] |
| - | [[Category: Sun, W]] | + | [[Category: Sun W]] |
| - | [[Category: Wang, Z Z]] | + | [[Category: Wang ZZ]] |
| - | [[Category: Xu, W Q]] | + | [[Category: Xu WQ]] |
| - | [[Category: Zhong, Q]] | + | [[Category: Zhong Q]] |
| - | [[Category: Zhu, Y]] | + | [[Category: Zhu Y]] |
| - | [[Category: Heat repeat]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Tumor suppressor]]
| + | |
| Structural highlights
Function
TSC1_SCHPO Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.[1] [2] [3]
Publication Abstract from PubMed
Tuberous sclerosis complex is a disease caused by mutations in two tumor-suppressor genes, TSC1 and TSC2. The TSC1 protein, also known as hamartin, has a critical role in controlling mTOR signalling. TSC1 does not bear apparent sequence homology with other proteins. Here we show that the N-terminal half of yeast TSC1 forms a protease-resistant domain, which is evolutionarily conserved. The crystal structure of this yeast TSC1 core domain shows that it contains a pseudo-HEAT repeat fold with its C-terminal end capped by a helical subdomain. This allows us to model the three-dimensional structure of the human TSC1 N-terminal domain (TSC1-NTD), which anchors essentially all pathogenic TSC1 missense mutations found in tuberous sclerosis patients. Interestingly, most pathogenic mutations map inside of the folded TSC1-NTD structure, whereas most non-pathogenic variants are on the structural surface. This indicates that the disruption of the TSC1-NTD globular structure is a major cause of tuberous sclerosis.
Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations.,Sun W, Zhu YJ, Wang Z, Zhong Q, Gao F, Lou J, Gong W, Xu W Nat Commun. 2013 Jul 16;4:2135. doi: 10.1038/ncomms3135. PMID:23857276[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Matsumoto S, Bandyopadhyay A, Kwiatkowski DJ, Maitra U, Matsumoto T. Role of the Tsc1-Tsc2 complex in signaling and transport across the cell membrane in the fission yeast Schizosaccharomyces pombe. Genetics. 2002 Jul;161(3):1053-63. PMID:12136010
- ↑ van Slegtenhorst M, Carr E, Stoyanova R, Kruger WD, Henske EP. Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe. J Biol Chem. 2004 Mar 26;279(13):12706-13. Epub 2004 Jan 12. PMID:14718525 doi:10.1074/jbc.M313874200
- ↑ Nakase Y, Fukuda K, Chikashige Y, Tsutsumi C, Morita D, Kawamoto S, Ohnuki M, Hiraoka Y, Matsumoto T. A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex. Genetics. 2006 Jun;173(2):569-78. Epub 2006 Apr 19. PMID:16624901 doi:10.1534/genetics.106.056895
- ↑ Sun W, Zhu YJ, Wang Z, Zhong Q, Gao F, Lou J, Gong W, Xu W. Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations. Nat Commun. 2013 Jul 16;4:2135. doi: 10.1038/ncomms3135. PMID:23857276 doi:10.1038/ncomms3135
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