title: Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding.
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.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Tewary
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Lynn
authors.affiliation: Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510, USA.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Cotmore
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Tattersall
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. Electronic address: zhaohy@ku.edu.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. Electronic address: tangl@ku.edu.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
mesh_terms: D000818:Animals; D001483:Base Sequence; D053904:DNA Breaks, Single-Stranded; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D051379:Mice; D008915:Minute Virus of Mice / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D010322:Parvoviridae Infections / Q000662:veterinary / Q000821:virology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018741:Replication Origin; D012376:Rodent Diseases / Q000821:virology; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C045264:replication initiator protein; D004265:DNA Helicases
keywords: DNA replication; Nickase; Non-structural protein 1; Nuclease; Parvovirus; Site-specific DNA binding