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

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 1.45 Å 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. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • Amore » single domain integrates multiple functions in virus replication.« less
Authors:
; ; ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [1]
  1. Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States)
  2. Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510 (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22470149
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 476; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CLEAVAGE; DNA; DNA REPLICATION; HISTIDINE; LIGANDS; METALS; MICE; NUCLEASES; ORIGIN; RESOLUTION; VIRUSES; VISIBLE RADIATION; X RADIATION