DEDDy 3'-5' exonuclease domain of yeast Rrp6p, human polymyositis/scleroderma autoantigen 100kDa, and similar proteins
Yeast Rrp6p and its human homolog, the polymyositis/scleroderma autoantigen 100kDa (PM/Scl-100), are exosome-associated proteins involved in the degradation and processing of precursors to stable RNAs. Both proteins contain a DEDDy-type DnaQ-like 3'-5' exonuclease domain possessing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific YX(3)D pattern at ExoIII. The motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. PM/Scl-100, an autoantigen present in the nucleolar compartment of the cell, reacts with autoantibodies produced by about 50% of patients with polymyositis-scleroderma overlap syndrome.
Comment:The catalytic site is characterized by the presence of four negatively charged residues (DEDD) that serve as ligands for the two metal ions required for activity.
Comment:DEDDy exonucleases contain a conserved tyrosine at the ExoIII motif which is important in catalysis.
Structure:2HBL_A; Saccharomyces cerevisiae Rrp6p binds Mn and Zn in its catalytic site.
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