Nucleic Acids Research Advance Access published online on August 2, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn497
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Nucleic Acid Enzymes |
The solution structure of the amino-terminal domain of human DNA polymerase 
subunit B is homologous to C-domains of AAA+ proteins
1Faculty of Biosciences, University of Joensuu, PO Box 111, FI-80101 Joensuu, 2NMR Laboratory, Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, PO Box 65, FI-00014 Helsinki, 3Department of Biochemistry, University of Oulu, PO Box 3000, FI-90014 Oulu, Finland and 4Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany
*To whom correspondence should be addressed. Tel: +1 49 3641 656297; Fax: +1 49 3641 656288; Email: pospiech{at}fli-leibniz.de
Received April 4, 2008. Revised June 13, 2008. Accepted July 19, 2008.
DNA polymerases 
, 
and 
are large multisubunit complexes that replicate the bulk of the DNA in the eukaryotic cell. In addition to the homologous catalytic subunits, these enzymes possess structurally related B subunits, characterized by a carboxyterminal calcineurin-like and an aminoproximal oligonucleotide/oligosaccharide binding-fold domain. The B subunits also share homology with the exonuclease subunit of archaeal DNA polymerases D. Here, we describe a novel domain specific to the N-terminus of the B subunit of eukaryotic DNA polymerases . The N-terminal domain of human DNA polymerases (Dpoe2NT) expressed in Escherichia coli was characterized. Circular dichroism studies demonstrated that Dpoe2NT forms a stable, predominantly -helical structure. The solution structure of Dpoe2NT revealed a domain that consists of a left-handed superhelical bundle. Four helices are arranged in two hairpins and the connecting loops contain short β-strand segments that form a short parallel sheet. DALI searches demonstrated a striking structural similarity of the Dpoe2NT with the -helical subdomains of ATPase associated with various cellular activity (AAA+) proteins (the C-domain). Like C-domains, Dpoe2NT is rich in charged amino acids. The biased distribution of the charged residues is reflected by a polarization and a considerable dipole moment across the Dpoe2NT. Dpoe2NT represents the first C-domain fold not associated with an AAA+ protein.