1u7f: Difference between revisions
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==Overview== | ==Overview== | ||
The formation of protein complexes between phosphorylated R-Smads and | 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. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Caestecker, M | [[Category: Caestecker, M de.]] | ||
[[Category: Chacko, B | [[Category: Chacko, B M.]] | ||
[[Category: Hayward, L | [[Category: Hayward, L J.]] | ||
[[Category: Lam, S.]] | [[Category: Lam, S.]] | ||
[[Category: Lin, K.]] | [[Category: Lin, K.]] | ||
[[Category: Qin, B | [[Category: Qin, B Y.]] | ||
[[Category: Shi, G.]] | [[Category: Shi, G.]] | ||
[[Category: Tiwari, A.]] | [[Category: Tiwari, A.]] | ||
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[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:21:21 2008'' | ||
Revision as of 13:21, 21 February 2008
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Crystal Structure of the phosphorylated Smad3/Smad4 heterotrimeric complex
Overview
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.
Disease
Known diseases associated with this structure: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome OMIM:[600993], Pancreatic cancer OMIM:[600993], Polyposis, juvenile intestinal OMIM:[600993]
About this Structure
1U7F is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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