Abstract: |
The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-β signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 Å resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue β hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-β- responsive genes. |
Keywords: |
signal transduction; gene mutation; mutation; dna-binding proteins; nonhuman; protein domain; smad3 protein; transforming growth factor beta; protein dna binding; cell transformation, neoplastic; dna; amino acid sequence; molecular sequence data; peptide fragments; crystal structure; dna sequence; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; trans-activators; protein structure; protein family; crystallization; protein structure, secondary; humans; priority journal; article
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