Figure 3

The proteomic organization of three subfamilies of Smads (C-Smad, R-Smad and I-Smad) and organization of a Smad MH1 domain with DNA. (a) All Smads information taken from PDB entry Smad>UniProt Gene list of Smads. The conserved N-terminal MH1 domain is in red, linker region in dark blue and the C-terminal MH2 domain in deep yellow. In the linker region the red PXS/TP (or S/TP) indicates the potential phosphorylation site for MAPKs ERK1/2, and the square indicates the PY (proline-tyrosine) motif that is recognized by the Hect/WW domain of Smurfs. The other domains and motifs are marked as follows: α-helix H1, H2, L3 and H3/4 loops, β–hairpin (β-h) that binds to DNA, the unique exon 3 of Smad2 (ex3), nuclear localization signal (NLS) and nuclear export signal (NES) motifs, Smad activation domain (SAD) at the linker-MH2 border. Sumoylation (sumo), ubiquitylation (ub), methylation (Me) and acetylation (Ac) sites are indicated with thundered heads. The unique SAD domain of Smad4 and the SSXS motif of R-Smads with asterisk indicating the phosphorylated serine residues. L3 loop and H1α helix in MH2 of Smad1, Smad5, Smad8 interacts with ALK1, ALK2, BMPR-IA, BMPR-IB by phosphorylation of Smad at C terminus. S*/T* indicate phosphorylatable serine and threonine residues. Brown S* phosphorylated by protein kinase C and by calmodulin-dependent kinase II. C-terminal red S*/S serines are phosphorylated by the type I receptor kinases. Different Smad interacting components, proteins and DNA with the specific functional domains of Smad are shown in the reviews by ten Dijke et al. (2000).⁸² (b) The 3D Java mol view of space filled secondary structure of a Smad MH1 domain bound to DNA (PDB entry 1MHD). Zoom in view represents the protein DNA interaction shows in red box. Highly conserved 11-residue β-hairpin loop recognizes major groove of DNA (dark blue) in a sequence-specific manner. In particular, β-hairpin loop in MH1 of Smad3, Smad4 interacts with 5″-AGAC-3″ termed Smad-binding elements.