Crystal structure of a Smad MH1 domain bound to DNA: Insights on DNA binding in TGF-β signaling Journal Article


Authors: Shi, Y.; Wang, Y. F.; Jayaraman, L.; Yang, H.; Massagué, J.; Pavletich, N. P.
Article Title: Crystal structure of a Smad MH1 domain bound to DNA: Insights on DNA binding in TGF-β signaling
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
Journal Title: Cell
Volume: 94
Issue: 5
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1998-09-04
Start Page: 585
End Page: 594
Language: English
DOI: 10.1016/s0092-8674(00)81600-1
PUBMED: 9741623
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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  1. Joan Massague
    388 Massague
  2. Haijuan Yang
    12 Yang