1u7f
From Proteopedia
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| , resolution 2.6Å | |||||||
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| Gene: | SMAD3, MADH3 (Homo sapiens), SMAD4, MADH4, DPC4 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the phosphorylated Smad3/Smad4 heterotrimeric complex
Contents |
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
Page seeded by OCA on Thu Mar 20 14:28:16 2008
