Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 9741623.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
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.
Medical subject headings
- DNA
- DNA-Binding Proteins
- Peptide Fragments
- Signal Transduction
- Trans-Activators
- Transforming Growth Factor beta