View source for 7co1


==Crystal structure of SMAD2 in complex with wild-type CBP==
<StructureSection load='7co1' size='340' side='right'caption='[[7co1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7co1]] 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=7CO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CO1 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]] 3.3&#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=7co1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7co1 OCA], [https://pdbe.org/7co1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7co1 RCSB], [https://www.ebi.ac.uk/pdbsum/7co1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7co1 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 ==
Transforming growth factor-beta (TGF-beta) proteins regulate multiple cellular functions, including cell proliferation, apoptosis, and extracellular matrix formation. The dysregulation of TGF-beta signaling causes diseases such as cancer and fibrosis, and therefore, understanding the biochemical basis of TGF-beta signal transduction is important for elucidating pathogenic mechanisms in these diseases. SMAD proteins are transcription factors that mediate TGF-beta signaling-dependent gene expression. The transcriptional coactivator CBP directly interacts with the MH2 domains of SMAD2 to activate SMAD complex-dependent gene expression. Here, we report the structural basis for CBP recognition by SMAD2. The crystal structures of the SMAD2 MH2 domain in complex with the SMAD2-binding region of CBP showed that CBP forms an amphiphilic helix on the hydrophobic surface of SMAD2. The expression of a mutated CBP peptide that showed increased SMAD2 binding repressed SMAD2-dependent gene expression in response to TGF-beta signaling in cultured cells. Disrupting the interaction between SMAD2 and CBP may therefore be a promising strategy for suppressing SMAD-dependent gene expression.

Structural basis for transcriptional coactivator recognition by SMAD2 in TGF-beta signaling.,Miyazono KI, Ito T, Fukatsu Y, Wada H, Kurisaki A, Tanokura M Sci Signal. 2020 Dec 15;13(662):eabb9043. doi: 10.1126/scisignal.abb9043. PMID:33323411<ref>PMID:33323411</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7co1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ito T]]
[[Category: Miyazono K]]
[[Category: Tanokura M]]
[[Category: Wada H]]