MH1 domain of Smad is a degraded homing endonuclease

Research output: Contribution to journalArticle

27 Scopus citations

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 languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalJournal of Molecular Biology
Volume307
Issue number1
DOIs
StatePublished - 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

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