Structural highlights
Function
[NS1_MUMIP] Multifunctional protein that plays an essential role in viral DNA replication. Inhibits the host cell cycle during the G1/S transition, the S-phase, and the G2/M transition. These arrests may provide essential cellular factors for viral DNA replication. Interacts specifically with the viral DNA origin of replication and plays a direct role in DNA replication. Participates in the transcriptional regulation of several promoters including the viral p38 promoter that regulates the expression of VP1 and VP2 transcripts. Promotes apoptosis in host cell.[1] [2] [3] [4]
Publication Abstract from PubMed
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 1.45A 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.
Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding.,Tewary SK, Liang L, Lin Z, Lynn A, Cotmore SF, Tattersall P, Zhao H, Tang L Virology. 2014 Dec 17;476C:61-71. doi: 10.1016/j.virol.2014.11.022. PMID:25528417[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Op De Beeck A, Sobczak-Thepot J, Sirma H, Bourgain F, Brechot C, Caillet-Fauquet P. NS1- and minute virus of mice-induced cell cycle arrest: involvement of p53 and p21(cip1). J Virol. 2001 Nov;75(22):11071-8. PMID:11602746 doi:http://dx.doi.org/10.1128/JVI.75.22.11071-11078.2001
- ↑ Mincberg M, Gopas J, Tal J. Minute virus of mice (MVMp) infection and NS1 expression induce p53 independent apoptosis in transformed rat fibroblast cells. Virology. 2011 Mar 30;412(1):233-43. doi: 10.1016/j.virol.2010.12.035. Epub 2011 , Feb 3. PMID:21295324 doi:http://dx.doi.org/10.1016/j.virol.2010.12.035
- ↑ Christensen J, Cotmore SF, Tattersall P. Minute virus of mice transcriptional activator protein NS1 binds directly to the transactivation region of the viral P38 promoter in a strictly ATP-dependent manner. J Virol. 1995 Sep;69(9):5422-30. PMID:7636987
- ↑ Op De Beeck A, Caillet-Fauquet P. The NS1 protein of the autonomous parvovirus minute virus of mice blocks cellular DNA replication: a consequence of lesions to the chromatin? J Virol. 1997 Jul;71(7):5323-9. PMID:9188601
- ↑ Tewary SK, Liang L, Lin Z, Lynn A, Cotmore SF, Tattersall P, Zhao H, Tang L. Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding. Virology. 2014 Dec 17;476C:61-71. doi: 10.1016/j.virol.2014.11.022. PMID:25528417 doi:http://dx.doi.org/10.1016/j.virol.2014.11.022
