Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling

Cell. 1998 Sep 4;94(5):585-94. doi: 10.1016/s0092-8674(00)81600-1.


The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-beta signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue beta 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-beta-responsive genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Transformation, Neoplastic / genetics
  • Crystallization
  • Crystallography, X-Ray
  • DNA / metabolism*
  • DNA / physiology
  • DNA-Binding Proteins / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptide Fragments / chemistry*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Signal Transduction / physiology*
  • Smad3 Protein
  • Trans-Activators / chemistry*
  • Transforming Growth Factor beta / physiology*


  • DNA-Binding Proteins
  • Peptide Fragments
  • SMAD3 protein, human
  • Smad3 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • DNA

Associated data

  • PDB/1MHD