Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling
The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-β signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 Å, and Smad2/Smad4 to 2.7 Å. Both complexes are heterotrimers, comprising two phos...
Gespeichert in:
| Veröffentlicht in: | Molecular cell 2004-09, Vol.15 (5), p.813-823 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 823 |
|---|---|
| container_issue | 5 |
| container_start_page | 813 |
| container_title | Molecular cell |
| container_volume | 15 |
| creator | Chacko, Benoy M. Qin, Bin Y. Tiwari, Ashutosh Shi, Genbin Lam, Suvana Hayward, Lawrence J. de Caestecker, Mark Lin, Kai |
| description | The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-β signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 Å, and Smad2/Smad4 to 2.7 Å. 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-β superfamily signaling. |
| doi_str_mv | 10.1016/j.molcel.2004.07.016 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66850214</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1097276504004381</els_id><sourcerecordid>66850214</sourcerecordid><originalsourceid>FETCH-LOGICAL-c404t-c2af8b4bbbc5fc3193c1ebd1f04bfedce00e64960f3c1feaba5527bc6140a6603</originalsourceid><addsrcrecordid>eNp9kN1KAzEQhYMotlbfQGSvvNt1ss1m2xuhFvsDBYXW65BkJyVlf2qyK_S1fBCfyZQWvPNqhplzzjAfIfcUEgqUP-2Sqik1lkkKwBLIkzC8IH0K4zxmlLPLc5_mPOuRG-93AJRlo_E16dFsmEGasj5ZrlvX6bZzsoxepLc-aky0wBZdU6GzOlpXsojeXdOiraOJ91ip8hCFfjOfxT_f0dpua1naentLrowsPd6d64B8zF4300W8epsvp5NVrBmwNtapNCPFlFI6M3pIx0NNURXUAFMGC40AyNmYgwkLg1LJLEtzpTllIDmH4YA8nnL3rvns0Leisj5wKGWNTecF56PwG2VByE5C7RrvHRqxd7aS7iAoiCNCsRMnhOKIUEAuwjDYHs75naqw-DOdmQXB80mA4csvi054bbHWWFiHuhVFY_-_8AsZ0YVH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66850214</pqid></control><display><type>article</type><title>Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via ScienceDirect (Elsevier)</source><source>Free Full-Text Journals in Chemistry</source><creator>Chacko, Benoy M. ; Qin, Bin Y. ; Tiwari, Ashutosh ; Shi, Genbin ; Lam, Suvana ; Hayward, Lawrence J. ; de Caestecker, Mark ; Lin, Kai</creator><creatorcontrib>Chacko, Benoy M. ; Qin, Bin Y. ; Tiwari, Ashutosh ; Shi, Genbin ; Lam, Suvana ; Hayward, Lawrence J. ; de Caestecker, Mark ; Lin, Kai</creatorcontrib><description>The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-β signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 Å, and Smad2/Smad4 to 2.7 Å. 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-β superfamily signaling.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2004.07.016</identifier><identifier>PMID: 15350224</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Biomarkers, Tumor ; COS Cells ; Crystallography, X-Ray ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Hot Temperature ; Macromolecular Substances ; Models, Molecular ; Molecular Conformation ; Phosphorylation ; Polymers - metabolism ; Protein Structure, Tertiary ; Protein Subunits - genetics ; Protein Subunits - metabolism ; Signal Transduction - physiology ; Smad2 Protein ; Smad3 Protein ; Temperature ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transforming Growth Factor beta - metabolism</subject><ispartof>Molecular cell, 2004-09, Vol.15 (5), p.813-823</ispartof><rights>2004 Cell Press</rights><rights>Copyright 2004 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-c2af8b4bbbc5fc3193c1ebd1f04bfedce00e64960f3c1feaba5527bc6140a6603</citedby><cites>FETCH-LOGICAL-c404t-c2af8b4bbbc5fc3193c1ebd1f04bfedce00e64960f3c1feaba5527bc6140a6603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molcel.2004.07.016$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15350224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chacko, Benoy M.</creatorcontrib><creatorcontrib>Qin, Bin Y.</creatorcontrib><creatorcontrib>Tiwari, Ashutosh</creatorcontrib><creatorcontrib>Shi, Genbin</creatorcontrib><creatorcontrib>Lam, Suvana</creatorcontrib><creatorcontrib>Hayward, Lawrence J.</creatorcontrib><creatorcontrib>de Caestecker, Mark</creatorcontrib><creatorcontrib>Lin, Kai</creatorcontrib><title>Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-β signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 Å, and Smad2/Smad4 to 2.7 Å. 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-β superfamily signaling.</description><subject>Animals</subject><subject>Biomarkers, Tumor</subject><subject>COS Cells</subject><subject>Crystallography, X-Ray</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Hot Temperature</subject><subject>Macromolecular Substances</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Phosphorylation</subject><subject>Polymers - metabolism</subject><subject>Protein Structure, Tertiary</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Smad2 Protein</subject><subject>Smad3 Protein</subject><subject>Temperature</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kN1KAzEQhYMotlbfQGSvvNt1ss1m2xuhFvsDBYXW65BkJyVlf2qyK_S1fBCfyZQWvPNqhplzzjAfIfcUEgqUP-2Sqik1lkkKwBLIkzC8IH0K4zxmlLPLc5_mPOuRG-93AJRlo_E16dFsmEGasj5ZrlvX6bZzsoxepLc-aky0wBZdU6GzOlpXsojeXdOiraOJ91ip8hCFfjOfxT_f0dpua1naentLrowsPd6d64B8zF4300W8epsvp5NVrBmwNtapNCPFlFI6M3pIx0NNURXUAFMGC40AyNmYgwkLg1LJLEtzpTllIDmH4YA8nnL3rvns0Leisj5wKGWNTecF56PwG2VByE5C7RrvHRqxd7aS7iAoiCNCsRMnhOKIUEAuwjDYHs75naqw-DOdmQXB80mA4csvi054bbHWWFiHuhVFY_-_8AsZ0YVH</recordid><startdate>20040910</startdate><enddate>20040910</enddate><creator>Chacko, Benoy M.</creator><creator>Qin, Bin Y.</creator><creator>Tiwari, Ashutosh</creator><creator>Shi, Genbin</creator><creator>Lam, Suvana</creator><creator>Hayward, Lawrence J.</creator><creator>de Caestecker, Mark</creator><creator>Lin, Kai</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040910</creationdate><title>Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling</title><author>Chacko, Benoy M. ; Qin, Bin Y. ; Tiwari, Ashutosh ; Shi, Genbin ; Lam, Suvana ; Hayward, Lawrence J. ; de Caestecker, Mark ; Lin, Kai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-c2af8b4bbbc5fc3193c1ebd1f04bfedce00e64960f3c1feaba5527bc6140a6603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biomarkers, Tumor</topic><topic>COS Cells</topic><topic>Crystallography, X-Ray</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Hot Temperature</topic><topic>Macromolecular Substances</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Phosphorylation</topic><topic>Polymers - metabolism</topic><topic>Protein Structure, Tertiary</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Smad2 Protein</topic><topic>Smad3 Protein</topic><topic>Temperature</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chacko, Benoy M.</creatorcontrib><creatorcontrib>Qin, Bin Y.</creatorcontrib><creatorcontrib>Tiwari, Ashutosh</creatorcontrib><creatorcontrib>Shi, Genbin</creatorcontrib><creatorcontrib>Lam, Suvana</creatorcontrib><creatorcontrib>Hayward, Lawrence J.</creatorcontrib><creatorcontrib>de Caestecker, Mark</creatorcontrib><creatorcontrib>Lin, Kai</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chacko, Benoy M.</au><au>Qin, Bin Y.</au><au>Tiwari, Ashutosh</au><au>Shi, Genbin</au><au>Lam, Suvana</au><au>Hayward, Lawrence J.</au><au>de Caestecker, Mark</au><au>Lin, Kai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2004-09-10</date><risdate>2004</risdate><volume>15</volume><issue>5</issue><spage>813</spage><epage>823</epage><pages>813-823</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>The formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-β signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 Å, and Smad2/Smad4 to 2.7 Å. 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-β superfamily signaling.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15350224</pmid><doi>10.1016/j.molcel.2004.07.016</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-2765 |
| ispartof | Molecular cell, 2004-09, Vol.15 (5), p.813-823 |
| issn | 1097-2765 1097-4164 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_66850214 |
| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier); Free Full-Text Journals in Chemistry |
| subjects | Animals Biomarkers, Tumor COS Cells Crystallography, X-Ray DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Hot Temperature Macromolecular Substances Models, Molecular Molecular Conformation Phosphorylation Polymers - metabolism Protein Structure, Tertiary Protein Subunits - genetics Protein Subunits - metabolism Signal Transduction - physiology Smad2 Protein Smad3 Protein Temperature Trans-Activators - genetics Trans-Activators - metabolism Transforming Growth Factor beta - metabolism |
| title | Structural Basis of Heteromeric Smad Protein Assembly in TGF-β Signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T00%3A23%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20Basis%20of%20Heteromeric%20Smad%20Protein%20Assembly%20in%20TGF-%CE%B2%20Signaling&rft.jtitle=Molecular%20cell&rft.au=Chacko,%20Benoy%20M.&rft.date=2004-09-10&rft.volume=15&rft.issue=5&rft.spage=813&rft.epage=823&rft.pages=813-823&rft.issn=1097-2765&rft.eissn=1097-4164&rft_id=info:doi/10.1016/j.molcel.2004.07.016&rft_dat=%3Cproquest_cross%3E66850214%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66850214&rft_id=info:pmid/15350224&rft_els_id=S1097276504004381&rfr_iscdi=true |