Format

Send to

Choose Destination
Virology. 2015 Feb;476:61-71. doi: 10.1016/j.virol.2014.11.022. Epub 2014 Dec 18.

Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding.

Author information

1
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
2
Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510, USA.
3
Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510, USA; Departments of Genetics, Yale University Medical School, New Haven, CT 06510, USA.
4
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. Electronic address: zhaohy@ku.edu.
5
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. Electronic address: tangl@ku.edu.

Abstract

Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase active site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins.

KEYWORDS:

DNA replication; Nickase; Non-structural protein 1; Nuclease; Parvovirus; Site-specific DNA binding

PMID:
25528417
PMCID:
PMC4699654
DOI:
10.1016/j.virol.2014.11.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center