|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structural of the TSC1-TBC1D7 complex== | | ==Crystal structural of the TSC1-TBC1D7 complex== |
| - | <StructureSection load='5ejc' size='340' side='right' caption='[[5ejc]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='5ejc' size='340' side='right'caption='[[5ejc]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ejc]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EJC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ejc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EJC 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]] 3.1Å</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=5ejc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ejc OCA], [http://pdbe.org/5ejc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ejc RCSB], [http://www.ebi.ac.uk/pdbsum/5ejc PDBsum]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ejc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ejc OCA], [https://pdbe.org/5ejc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ejc RCSB], [https://www.ebi.ac.uk/pdbsum/5ejc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ejc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/TSC1_HUMAN TSC1_HUMAN]] Lymphangioleiomyomatosis;Tuberous sclerosis;Isolated focal cortical dysplasia type IIb. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TBCD7_HUMAN TBCD7_HUMAN]] Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question.<ref>PMID:22795129</ref> [[http://www.uniprot.org/uniprot/TSC1_HUMAN TSC1_HUMAN]] In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling.<ref>PMID:12271141</ref> <ref>PMID:15340059</ref> | + | [https://www.uniprot.org/uniprot/TBCD7_HUMAN TBCD7_HUMAN] Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question.<ref>PMID:22795129</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gong, W]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Qin, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, Z]] | + | [[Category: Gong W]] |
| - | [[Category: Xu, W]]
| + | [[Category: Qin J]] |
| - | [[Category: Signaling protein]] | + | [[Category: Wang Z]] |
| - | [[Category: Tbc1d7]] | + | [[Category: Xu W]] |
| - | [[Category: Tsc1]] | + | |
| Structural highlights
Function
TBCD7_HUMAN Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question.[1]
Publication Abstract from PubMed
Mutations in TSC1 or TSC2 cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by the occurrence of benign tumors in various vital organs and tissues. TSC1 and TSC2, the TSC1 and TSC2 gene products, form the TSC protein complex that senses specific cellular growth conditions to control mTORC1 signaling. TBC1D7 is the third subunit of the TSC complex, and helps to stabilize the TSC1-TSC2 complex through its direct interaction with TSC1. Homozygous inactivation of TBC1D7 causes intellectual disability and megaencephaly. Here we report the crystal structure of a TSC1-TBC1D7 complex and biochemical characterization of the TSC1-TBC1D7 interaction. TBC1D7 interacts with the C-terminal region of the predicted coiled-coil domain of TSC1. The TSC1-TBC1D7 interface is largely hydrophobic, involving the alpha4 helix of TBC1D7. Each TBC1D7 protein interacts simultaneously with two parallel TSC1 helices from two TSC1 molecules, suggesting that TBC1D7 may stabilize the TSC complex by tethering the C-terminal ends of two TSC1 coiled-coils.
Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7).,Qin J, Wang Z, Hoogeveen-Westerveld M, Shen G, Gong W, Nellist M, Xu W J Biol Chem. 2016 Feb 18. pii: jbc.M115.701870. PMID:26893383[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dibble CC, Elis W, Menon S, Qin W, Klekota J, Asara JM, Finan PM, Kwiatkowski DJ, Murphy LO, Manning BD. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell. 2012 Aug 24;47(4):535-46. doi: 10.1016/j.molcel.2012.06.009. Epub 2012 , Jul 12. PMID:22795129 doi:10.1016/j.molcel.2012.06.009
- ↑ Qin J, Wang Z, Hoogeveen-Westerveld M, Shen G, Gong W, Nellist M, Xu W. Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7). J Biol Chem. 2016 Feb 18. pii: jbc.M115.701870. PMID:26893383 doi:http://dx.doi.org/10.1074/jbc.M115.701870
|
