An iteron-related domain is associated to Motif 1 in the replication proteins of geminiviruses: identification of potential interacting amino acid-base pairs by a comparative approach

Geminiviruses encode a replication initiator protein, Rep, which binds in a sequence-specific fashion to iterated DNA motifs (iterons) functioning as essential elements for virus-specific replication. By using the iterons of more than one hundred geminiviruses as heuristic devices, we have identifie d a Rep subdomain 8 to 10 residues in length, whose primary structure varie s among viruses harboring different iterons, but which is similar among vir uses with identical iterons, regardless of their differences in host range, insect vector, geographical origin or genome structure. Close analysis of this heron-related domain (IRD) revealed consistent correlations between sp ecific Rep residues and defined nucleotides of its cognate iteron, thus pro viding important insights about the molecular code which dictates the Rep p reference for specific DNA sequences. A model of potential Rep-iteron conta cts is proposed. The identified IRD is adjacent to a conserved motif charac teristic of a superfamily of rolling-circle (RC) replication proteins, and secondary structure predictions suggest that those Rep subdomains form toge ther the core of a novel DNA-binding domain possessing a beta -sheet as rec ognition subdomain, which is apparently conserved in the replication protei ns of nanoviruses, circoviruses, microviruses, and a variety of ssDNA plasm ids of eubacteria, archaebacteria and red algae. The evolutionary implicati ons of these findings are discussed.