title: The human parvovirus B19 non-structural protein 1 N-terminal domain specifically binds to the origin of replication in the viral DNA.
abstract: The non-structural protein 1 (NS1) of human parvovirus B19 plays a critical role in viral DNA replication. Previous studies identified the origin of replication in the viral DNA, which contains four DNA elements, namely NSBE1 to NSBE4, that are required for optimal viral replication (Guan et al., 2009). Here we have demonstrated in vitro that the NS1 N-terminal domain (NS1N) binds to the origin of replication in a sequence-specific, length-dependent manner that requires NSBE1 and NSBE2, while NSBE3 and NSBE4 are dispensable. Mutagenesis analysis has identified nucleotides in NSBE1 and NSBE2 that are critical for NS1N binding. These results suggest that NS1 binds to the NSBE1-NSBE2 region in the origin of replication, while NSBE3 and NSBE4 may provide binding sites for potential cellular factors. Such a specialized nucleoprotein complex may enable NS1 to nick the terminal resolution site and separate DNA strands during replication.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Tewary
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA. Electronic address: tangl@ku.edu.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006801:Humans; D010322:Parvoviridae Infections / Q000821:virology*; D016732:Parvovirus B19, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018741:Replication Origin; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D017361:Viral Nonstructural Proteins
keywords: B19; Non-structural protein 1; Origin of replication; Parvovirus; Protein:DNA interaction