Abstract
Smad proteins are eukarytic transcription regulators in the TGF-β signaling cascade. Using a combination of sequence and structure-based analyses, we argue that MH1 domain of Smad is homologous to the diverse His-Me finger endonuclease family enzymes. The similarity is particularly extensive with the I-PpoI endonuclease. In addition to the global fold similarities, both proteins possess a conserved motif of three cysteine residues and one histidine residue which form a zinc-binding site in I-PpoI. Sequence and structure conservation in the motif region strongly suggest that MH1 domain may also incorporate a metal ion in its structural core. MH1 of Smad3 and I-PpoI exhibit similar nucleic acid binding mode and interact with DNA major groove through an antiparallel β-sheet. MH1 is an example of transcription regulator derived from the ancient enzymatic domain that lost its catalytic activity but retained DNA-binding sites.
Original language | English (US) |
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Pages (from-to) | 31-37 |
Number of pages | 7 |
Journal | Journal of Molecular Biology |
Volume | 307 |
Issue number | 1 |
DOIs | |
State | Published - Mar 16 2001 |
Keywords
- Cys-His box
- Dwarfins
- HNH motif
- His-Me finger endonucleases
- Protein structure classification
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology