Abstract
Eukaryotic ssDNA viruses encode a rolling-circle replication (RCR) initiation protein, Rep, which binds to iterated DNA elements functioning as essential elements for virus-specific replication. By using the iterons of all known circoviruses, nanoviruses and nanovirus-like satellites as heuristic devices, we have identified certain amino acid residues that presumably determine the DNA-binding specificity of their Rep proteins. These putative “specificity determinants” (SPDs) cluster in two discrete protein regions, which are adjacent to distinct conserved motifs. A comparable distribution of SPDs was uncovered in the Rep protein of geminiviruses. Modeling of the tertiary structure of diverse Rep proteins showed that SPD regions interact to form a small β-sheet element that has been proposed to be critical for high-affinity DNA-binding of Rep. Our findings indicate that eukaryotic circular ssDNA viruses have a common ancestor and suggest that SPDs present in replication initiators from a huge variety of viral and plasmid RCR systems are associated with the same conserved motifs.
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Acknowledgments
We thank Drs. Roberto Ruiz-Medrano (CINVESTAV, IPN), José Trinidad Ascencio-Ibañez (North Carolina State University) and Braulio Gutiérrez-Medina (IPICYT) for critical reading of the manuscript and many helpful suggestions. A.L. was supported by a fellowship from the Instituto Potosino de Investigación Científica y Tecnológica, A.C., and a PhD fellowship (211758) from CONACYT, Mexico. This research was supported by the Consejo Nacional de Ciencia y Tecnología, Mexico (grant no. 42639-Q to G.R.A.-A. and grant no. 49039 to L.R.-R).
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Londoño, A., Riego-Ruiz, L. & Argüello-Astorga, G.R. DNA-binding specificity determinants of replication proteins encoded by eukaryotic ssDNA viruses are adjacent to widely separated RCR conserved motifs. Arch Virol 155, 1033–1046 (2010). https://doi.org/10.1007/s00705-010-0674-4
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DOI: https://doi.org/10.1007/s00705-010-0674-4