Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling
- PMID: 9741623
- DOI: 10.1016/s0092-8674(00)81600-1
Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling
Abstract
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.
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