1u7v

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==Overview==
==Overview==
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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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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]]
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[[Category: Caestecker, M.de.]]
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[[Category: Caestecker, M de.]]
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[[Category: Chacko, B.M.]]
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[[Category: Chacko, B M.]]
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[[Category: Hayward, L.J.]]
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[[Category: Hayward, L J.]]
[[Category: Lam, S.]]
[[Category: Lam, S.]]
[[Category: Lin, K.]]
[[Category: Lin, K.]]
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[[Category: Qin, B.Y.]]
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[[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]]
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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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:21:29 2008''

Revision as of 13:21, 21 February 2008


1u7v, resolution 2.7Å

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Crystal Structure of the phosphorylated Smad2/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

1U7V 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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