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1u7v

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[[Image:1u7v.jpg|left|200px]]<br /><applet load="1u7v" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1u7v, resolution 2.7&Aring;" />
 
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'''Crystal Structure of the phosphorylated Smad2/Smad4 heterotrimeric complex'''<br />
 
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==Overview==
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==Crystal Structure of the phosphorylated Smad2/Smad4 heterotrimeric complex==
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The formation of protein complexes between phosphorylated R-Smads and, Smad4 is a central event in the TGF-beta signaling pathway. We have, determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 angstroms, and Smad2/Smad4 to 2.7 angstroms. Both, complexes are heterotrimers, comprising two phosphorylated R-Smad subunits, and one Smad4 subunit, a finding that was corroborated by isothermal, titration calorimetry and mutational studies. Preferential formation of, the R-Smad/Smad4 heterotrimer over the R-Smad homotrimer is largely, enthalpy driven, contributed by the unique presence of strong, electrostatic interactions within the heterotrimeric interfaces. The study, supports a common mechanism of Smad protein assembly in TGF-beta, superfamily signaling.
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<StructureSection load='1u7v' size='340' side='right'caption='[[1u7v]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1u7v]] is a 3 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=1U7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U7V FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u7v OCA], [https://pdbe.org/1u7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u7v RCSB], [https://www.ebi.ac.uk/pdbsum/1u7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u7v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u7/1u7v_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1u7v ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-beta signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 angstroms, and Smad2/Smad4 to 2.7 angstroms. Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. Preferential formation of the R-Smad/Smad4 heterotrimer over the R-Smad homotrimer is largely enthalpy driven, contributed by the unique presence of strong electrostatic interactions within the heterotrimeric interfaces. The study supports a common mechanism of Smad protein assembly in TGF-beta superfamily signaling.
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==Disease==
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Structural basis of heteromeric smad protein assembly in TGF-beta signaling.,Chacko BM, Qin BY, Tiwari A, Shi G, Lam S, Hayward LJ, De Caestecker M, Lin K Mol Cell. 2004 Sep 10;15(5):813-23. PMID:15350224<ref>PMID:15350224</ref>
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Known diseases associated with this structure: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]], Polyposis, juvenile intestinal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600993 600993]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1U7V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U7V OCA].
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</div>
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<div class="pdbe-citations 1u7v" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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Structural basis of heteromeric smad protein assembly in TGF-beta signaling., Chacko BM, Qin BY, Tiwari A, Shi G, Lam S, Hayward LJ, De Caestecker M, Lin K, Mol Cell. 2004 Sep 10;15(5):813-23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15350224 15350224]
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Caestecker, M.de.]]
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[[Category: Chacko BM]]
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[[Category: Chacko, B.M.]]
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[[Category: Hayward LJ]]
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[[Category: Hayward, L.J.]]
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[[Category: Lam S]]
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[[Category: Lam, S.]]
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[[Category: Lin K]]
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[[Category: Lin, K.]]
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[[Category: Qin BY]]
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[[Category: Qin, B.Y.]]
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[[Category: Shi G]]
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[[Category: Shi, G.]]
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[[Category: Tiwari A]]
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[[Category: Tiwari, A.]]
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[[Category: De Caestecker M]]
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[[Category: phosphorylation]]
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[[Category: protein complex]]
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[[Category: signal transduction]]
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[[Category: smad]]
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[[Category: tgf-beta]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:59:33 2008''
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Current revision

Crystal Structure of the phosphorylated Smad2/Smad4 heterotrimeric complex

PDB ID 1u7v

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