View source for 5xod


==Crystal structure of human Smad2-Ski complex==
<StructureSection load='5xod' size='340' side='right'caption='[[5xod]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xod]] is a 2 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=5XOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XOD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.851&#8491;</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=5xod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xod OCA], [https://pdbe.org/5xod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xod RCSB], [https://www.ebi.ac.uk/pdbsum/5xod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xod ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SMAD2_HUMAN SMAD2_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 SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.<ref>PMID:9892009</ref> <ref>PMID:16751101</ref> <ref>PMID:17327236</ref> <ref>PMID:16862174</ref> <ref>PMID:19289081</ref> 
<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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xod" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ito T]]
[[Category: Miyazono K]]
[[Category: Moriwaki S]]
[[Category: Tanokura M]]