3gmj | pdb_00003gmj
Crystal structure of MAD MH2 domain
Structural highlights
Function[MAD_DROME] Required for the function of decapentaplegic. May play an important role in mediating Dpp signaling. Involved in the BMP signaling pathway.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Crystal structure of the MH2 domain of Drosophila Mad.,WANG C, CHEN L, WANG L, WU J Sci China C Life Sci. 2009 Jun;52(6):539-44. Epub 2009 Jun 26. PMID:19557331[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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