5xoc
From Proteopedia
(Difference between revisions)
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<StructureSection load='5xoc' size='340' side='right' caption='[[5xoc]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='5xoc' size='340' side='right' caption='[[5xoc]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5xoc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XOC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XOC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xoc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XOC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XOC FirstGlance]. <br> |
| - | </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=5xoc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xoc OCA], [http://pdbe.org/5xoc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xoc RCSB], [http://www.ebi.ac.uk/pdbsum/5xoc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xoc ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMAD3, MADH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FOXH1, FAST1, FAST2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5xoc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xoc OCA], [http://pdbe.org/5xoc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xoc RCSB], [http://www.ebi.ac.uk/pdbsum/5xoc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xoc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SMAD3_HUMAN SMAD3_HUMAN]] Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.<ref>PMID:9732876</ref> <ref>PMID:9892009</ref> <ref>PMID:10995748</ref> <ref>PMID:15241418</ref> <ref>PMID:15588252</ref> <ref>PMID:16156666</ref> <ref>PMID:16751101</ref> <ref>PMID:17327236</ref> <ref>PMID:16862174</ref> <ref>PMID:19289081</ref> <ref>PMID:19218245</ref> [[http://www.uniprot.org/uniprot/THIO_ECOLI THIO_ECOLI]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. | [[http://www.uniprot.org/uniprot/SMAD3_HUMAN SMAD3_HUMAN]] Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.<ref>PMID:9732876</ref> <ref>PMID:9892009</ref> <ref>PMID:10995748</ref> <ref>PMID:15241418</ref> <ref>PMID:15588252</ref> <ref>PMID:16156666</ref> <ref>PMID:16751101</ref> <ref>PMID:17327236</ref> <ref>PMID:16862174</ref> <ref>PMID:19289081</ref> <ref>PMID:19218245</ref> [[http://www.uniprot.org/uniprot/THIO_ECOLI THIO_ECOLI]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transforming growth factor-beta (TGF-beta) superfamily of cytokines regulates various biological processes, including cell proliferation, immune responses, autophagy, and senescence. Dysregulation of TGF-beta signaling causes various diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription factors involved in TGF-beta signaling, and they form heterotrimeric complexes with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in response to TGF-beta signaling. These heterotrimeric complexes interact with cofactors to control the expression of TGF-beta-dependent genes. SMAD2 and SMAD3 may promote or repress target genes depending on whether they form complexes with other transcription factors, coactivators, or corepressors; therefore, the selection of specific cofactors is critical for the appropriate activity of these transcription factors. To reveal the structural basis by which SMAD2 and SMAD3 select cofactors, we determined the crystal structures of SMAD3 in complex with the transcription factor FOXH1 and SMAD2 in complex with the transcriptional corepressor SKI. The structures of the complexes show that the MAD homology 2 (MH2) domains of SMAD2 and SMAD3 have multiple hydrophobic patches on their surfaces. The cofactors tether to various subsets of these patches to interact with SMAD2 and SMAD3 in a cooperative or competitive manner to control the output of TGF-beta signaling. | ||
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| + | Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors.,Miyazono KI, Moriwaki S, Ito T, Kurisaki A, Asashima M, Tanokura M Sci Signal. 2018 Mar 27;11(523). pii: 11/523/eaao7227. doi:, 10.1126/scisignal.aao7227. PMID:29588413<ref>PMID:29588413</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5xoc" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Ito, T]] | [[Category: Ito, T]] | ||
[[Category: Miyazono, K]] | [[Category: Miyazono, K]] | ||
Revision as of 14:11, 11 April 2018
Crystal structure of human Smad3-FoxH1 complex
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