PROSITE logo

PROSITE documentation PDOC52022
Parvovirus (PV) NS1 nuclease (NS1-Nuc) domain profile


Description

The family Parvoviridae is a group of small (1826nm diameter), non-enveloped, and autonomously replicating icosahedral viruses containing a single-stranded linear DNA genome ranging from 4-6 kb in length, with terminal hairpins [E1]. The parvoviral single-stranded DNA genome contains two open reading frames (ORFs), one encoding nonstructural (NS) proteins, the other capsid proteins. All parvoviruses encode a nonstructural protein NS1 (termed Rep in adeno-associated virus [AAV]) that is essential for viral DNA replication and packaging of viral DNA into capsid. It may play other versatile roles, for example, in the transactivation of viral and cellular gene expression, DNA damage response, cell cycle arrest, apoptosis, and/or the modulation of innate immunity. The N-terminus of the parvoviral NS1 protein contains an origin of replication binding (OBD) domain, also known as a DNA-specific binding domain or nuclease (NS1-Nuc) domain. Its central region contains a helicase domain (see <PDOC51206>), which includes an NTP-binding site, and its C-terminus includes a transactivation domain (TAD). The PV NS1-Nuc domain plays an important role in the "rolling hairpin" replication of the single-stranded parvoviral DNA genome: after cellular enzymes have converted the viral genome into double-stranded DNA, it recognizes origin of replication sequences and cleaves (i.e., nicks) one strand DNA at a nearby site known as the terminal resolution site (trs). Since the DNA encountered by NS1 is double-stranded, it is assumed that binding of NS1 to its target sequences induces strand separation, allowing for the endonuclease activity of NS1 to cleave at the trs site [1,2,3,4,5,6,7]. A homologue of parvoviral NS1, U94, is found in human herpesvirus 6 variants A and B (HHV-6A and HHV-6B, respectively) which do not replicate by "rolling hairpin" mecanism. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation [8,9].

The PV NS1-Nuc domain consists of a central five-stranded antiparallel β-sheet surrounded by clusters of α-helices (see <PDB:4KW3>. The central β-sheet forms a cleft that embraces the endonuclease active site. The NS1-Nuc domain structure reveals an overall fold that is canonical to the HUH superfamily of endonucleases that are involved in rolling-circle replication, which contain signature motif HUH, also known as motif 2, and motif YUxxYx(2-3)K, also known as motif 3 (where Y is tyrosine, U is hydrophobic residue, x is any residue, and K is lysine). Divalent metal ions are required for DNA cleavage activities for the HUH-superfamily of endonucleases. The catalytic center of HUH-endonucleases is composed of four residues. Unlike the two characteristic Histidine residues, the third catalytic residue is changeable (either Glu or His). The fourth residue is a Tyrosine, which is highly conserved in HUH-endonucleases [2,3,4,5,6,7].

The profile we developed covers the entire PV NS1-Nuc domain.

Last update:

May 2023 / First entry.

-------------------------------------------------------------------------------


Technical section

PROSITE method (with tools and information) covered by this documentation:

PV_NS1_NUC, PS52022; Parvovirus (PV) NS1 nuclease (NS1-Nuc) domain profile  (MATRIX)


References

1AuthorsXie Q. Wang J. Gu C. Wu J. Liu W.
TitleStructure and function of the parvoviral NS1 protein: a review.
SourceVirus. Genes. 59:195-203(2023).
PubMed ID36253516
DOI10.1007/s11262-022-01944-2

2AuthorsTang S. Song X. Xue L. Wang X. Wang X. Xu P. Ren G.
TitleCharacterization and Distribution Analysis of a Densovirus Infecting Myzus persicae nicotianae (Hemiptera: Aphididae).
SourceJ. Econ. Entomol. 109:580-587(2016).
PubMed ID26791818
DOI10.1093/jee/tov399

3AuthorsHickman A.B. Ronning D.R. Kotin R.M. Dyda F.
TitleStructural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep.
SourceMol. Cell. 10:327-337(2002).
PubMed ID12191478
DOI10.1016/s1097-2765(02)00592-0

4AuthorsTewary S.K. Zhao H. Shen W. Qiu J. Tang L.
TitleStructure of the NS1 protein N-terminal origin recognition/nickase domain from the emerging human bocavirus.
SourceJ. Virol. 87:11487-11493(2013).
PubMed ID23966383
DOI10.1128/JVI.01770-13

5AuthorsTewary S.K. Liang L. Lin Z. Lynn A. Cotmore S.F. Tattersall P. Zhao H. Tang L.
TitleStructures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding.
SourceVirology 476:61-71(2015).
PubMed ID25528417
DOI10.1016/j.virol.2014.11.022

6AuthorsZhang Y. Shao Z. Gao Y. Fan B. Yang J. Chen X. Zhao X. Shao Q. Zhang W. Cao C. Liu H. Gan J.
TitleStructures and implications of the nuclease domain of human parvovirus B19 NS1 protein.
SourceComput. Struct. Biotechnol. J. 20:4645-4655(2022).
PubMed ID36090819
DOI10.1016/j.csbj.2022.08.047

7AuthorsSanchez J.L. Ghadirian N. Horton N.C.
TitleHigh-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1.
SourceJ. Virol. 96:E0216421-E0216421(2022).
PubMed ID35435730
DOI10.1128/jvi.02164-21

8AuthorsRapp J.C. Krug L.T. Inoue N. Dambaugh T.R. Pellett P.E.
TitleU94, the human herpesvirus 6 homolog of the parvovirus nonstructural gene, is highly conserved among isolates and is expressed at low mRNA levels as a spliced transcript.
SourceVirology 268:504-516(2000).
PubMed ID10704358
DOI10.1006/viro.1999.0163

9AuthorsCaselli E. D'Accolti M. Caccuri F. Soffritti I. Gentili V. Bortolotti D. Rotola A. Cassai E. Fiorentini S. Zani A. Caruso A. Rizzo R. Di Luca D.
SourceThe U94 Gene of Human Herpesvirus 6: A Narrative Review of Its Role and Potential Functions. Cells 9:0-0(2020).
PubMed ID33291793
DOI10.3390/cells9122608

E1Titlehttps://viralzone.expasy.org/103



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)