3GMJ

Crystal structure of MAD MH2 domain

Summary for 3GMJ

• Entry DOI: 10.2210/pdb3gmj/pdb
• Descriptor: Protein mothers against dpp (2 entities in total)
• Functional Keywords: mh2, smad, mad, cytoplasm, developmental protein, nucleus, phosphoprotein, transcription, transcription regulation, ubl conjugation
• Biological source: Drosophila melanogaster (Fruit fly)
• Cellular location: Cytoplasm: P42003
• Total number of polymer chains: 4
• Total formula weight: 108260.22

Authors

Wu, J.W.,Wang, C. (deposition date: 2009-03-14, release date: 2009-12-15, Last modification date: 2024-03-20)

Primary citation

Wang, C.,Chen, L.,Wang, L.,Wu, J.W.
Crystal structure of the MH2 domain of Drosophila Mad
SCI.CHINA, SER.C: LIFE SCI., 52:539-544, 2009

PubMed Abstract: The decapentaplegic(Dpp), a member of the TGF-beta superfamily, plays a pivotal role in the control of proliferation, global patterning and induction of specific cell fates during Drosophila development. Mother against Dpp(Mad) is the founding member of the conserved Smad protein family which specifically transduces the intracellular TGF-beta signaling cascade. Here we report the 2.80 A structure of the MH2 domain of Mad(Mad-MH2) that was readily superposed to the mammal Smad-MH2 structures. This unphosphorylated Mad-MH2 forms a symmetric homotrimer in crystals, consistent with the result of the size-exclusion chromatography that Mad-MH2 exhibited a propensity for concentration-dependent oligomerization prior to phosphorylation. Structural analysis revealed that the formation of homotrimeric Mad-MH2 is mainly mediated by contacts involving the extreme C-terminal SSVS motif, and is strengthened by phosphorylation of the last two Ser residues which was confirmed by the gel filtration analysis of the pseudophosphorylated Mad-MH2(DVD). Intriguingly, the homotrimer within an asymmetric unit only possesses two ordered C-terminal tails, reminiscent of the arrangement of the R-Smad/Smad4 complexes, indicating that the subunit with a flexible SSXS motif would be readily replaced by Co-Smad to form a functional heterotrimer.

PubMed: 19557331
DOI: 10.1007/s11427-009-0080-x

Experimental method

X-RAY DIFFRACTION (2.8 Å)