DNA Mimicry by Antirestriction and Pentapeptide Repeat (PPR) Proteins

Protein mimicry of DNA is a recently discovered direct mechanism of regulation of DNAdependent enzyme activity by means of proteins that mimic DNA structure and interact with a target enzyme and completely inhibit (or modulate) its activity. DNA-mimicking inhibitor proteins bind directly to the enzyme and thus blocks or alters the activity of the latter. Protein mimicry of DNA was first described in Ugi derived from PBS2 bacteriophage of Bacillus subtilis (Mol et al, 1995). This protein of 84 amino acid residues with a total charge of (–12) inhibits uracil-DNA glycosylase (UDG), an enzyme involved in DNA repair (Mol et al, 1995; Putnam & Tainer, 2005). Subsequently, this type of protein mimicry was found in the ribosomal elongation factor EF-G (tRNA-like motif), and in the dTAFII 230 component of eukaryotic transcription factor TFIID (DNA-like domain) (Liu et al., 1998). The family of DNA mimetics further includes DinI, a negative SOS response regulator in E. coli (Ramirez et al., 2000), and a nucleosome forming protein HI1450 of Haemophilus influenzae (Parsons et al., 2004). However, in most of these cases, only a part of the protein molecule is DNA-like, in contrast to antirestriction and pentapeptide repeat (PPR) proteins, whose entire structure mimics the B-form of DNA. For instance, the X-ray structure of Ugi reveals a domain similar to the B-form of DNA, but the molecule as a whole is globular. Note that, in Ugi, the crucial negative charges are those of E20, E28, and E31 in the N domain (Mol et al.,1995).