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

Tewary, Sunil Kumar; Liang, Lingfei; Lin, Zihan; Lynn, Anna Y.; Cotmore, Susan F.; Tattersall, Peter; Zhao, Haiyan; Tang, Liang

doi:10.1016/j.virol.2014.11.022

Cited by 15 publications

(9 citation statements)

References 57 publications

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“…If these were considered, then the metal-binding range would increase to include Hg 2+ , Ca 2+ , Cd 2+ , and Cu 2+ . This promiscuity in divalent metal-binding is consistent with observations made with several HUH endonucleases, such as the TrwC relaxase, which can bind to Cu 2+ , Ni 2+ , and Zn 2+ [15] and the MVM NS1 protein, which can bind to Co 2+ , Cu 2+ , Ni 2+ , Mg 2+ , Mn 2+ , and Zn 2+ [16].…”

Section: Prediction Of the Sirv1 Rep Metal-binding Sitesupporting

confidence: 89%

“…Most of the differences occur on both ARV sequences, where there is a stretch of positively charged sequences ranging from Lys‐46 to Lys‐57, which is more pronounced in ARV2 (K 46 KGKKKRKRKTK 57 ), precedes the putative DNA binding region described previously, and is not present in the other sequences. A similar but shorter stretch of basic amino acids occurs in the MVM , HboV , and AAV5 Rep proteins , and forms a loop, which inserts in the major groove of the 26‐mer dsDNA as seen in the AAV5 Rep197‐26 mer dsDNA complex structure. Although it is plausible that these ARV basic residues may also form a loop, a definitive answer can only be provided upon structural characterization of the ARV proteins.…”

Section: Resultsmentioning

confidence: 95%

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Design and implementation of structural bioinformatics projects for biological sciences undergraduate students

Oke

Agbalajobi

Osifeso

et al. 2018

Biochem Molecular Bio Educ

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Contemporary biology is currently undergoing a revolution, driven by the availability of high‐throughput technologies and a wide variety of bioinformatics tools. However, bioinformatics education and practice is still in its infancy in most of the African continent. Consequently, concerted efforts have been made in recent years to incorporate bioinformatics modules into biological sciences curriculum of African Universities. Despite this, one aspect of bioinformatics that is yet to be incorporated is structural bioinformatics. In this article, we report on a structural bioinformatics project carried out by final year project students in a Nigerian university. The target protein was the thermoacidophilic Sulfolobus islandicus rod‐shaped virus 1 (SIRV1) Rep protein, which was further characterized using various free, user‐friendly and online sequence‐based and structure‐based bioinformatics tools. This exercise gave students the opportunity to generate new data, interpret the data, and acquire collaborative research skills. In this report, emphasis is placed on analysis of the data generated to further encourage analytical skills. By sharing this experience, it is anticipated that other similar institutions would adopt parallel strategies to expose undergraduate students to structural biology, and increase awareness of freely available bioinformatics tools for tackling pertinent biological questions. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):547–554, 2018.

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Section: Prediction Of the Sirv1 Rep Metal-binding Sitesupporting

confidence: 89%

Section: Resultsmentioning

confidence: 95%

Design and implementation of structural bioinformatics projects for biological sciences undergraduate students

Oke

Agbalajobi

Osifeso

et al. 2018

Biochem Molecular Bio Educ

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show abstract

“…Mutation of the two histidine residues (H115 and H117) confirmed their nicking function. A study of the structure of the MVM NS1 OBD also revealed conserved residues with DNA binding and nicking activities (45), highlighting the importance of the confirmed DNA binding and nicking residues of the HBoV1 NS1 OBD.…”

Section: Discussionmentioning

confidence: 96%

Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome

Shen

Deng

Zou

et al. 2016

J Virol

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Parvoviruses are single-stranded DNA viruses that use the palindromic structures at the ends of the viral genome for their replication. The mechanism of parvovirus replication has been studied mostly in the dependoparvovirus adeno-associated virus 2 (AAV2) and the protoparvovirus minute virus of mice (MVM). Here, we used human bocavirus 1 (HBoV1) to understand the replication mechanism of bocaparvovirus. HBoV1 is pathogenic to humans, causing acute respiratory tract infections, especially in young children under 2 years old. By using the duplex replicative form of the HBoV1 genome in human embryonic kidney 293 (HEK293) cells, we identified the HBoV1 minimal replication origin at the right-end hairpin (OriR). Mutagenesis analyses confirmed the putative NS1 binding and nicking sites within the OriR. Of note, unlike the large nonstructural protein (Rep78/68 or NS1) of other parvoviruses, HBoV1 NS1 did not specifically bind OriR in vitro, indicating that other viral and cellular components or the oligomerization of NS1 is required for NS1 binding to the OriR. In vivo studies demonstrated that residues responsible for NS1 binding and nicking are within the origin-binding domain. Further analysis identified that the small nonstructural protein NP1 is required for HBoV1 DNA replication at OriR. NP1 and other viral nonstructural proteins (NS1 to NS4) colocalized within the viral DNA replication centers in both OriR-transfected cells and virus-infected cells, highlighting a direct involvement of NP1 in viral DNA replication at OriR. Overall, our study revealed the characteristics of HBoV1 DNA replication at OriR, suggesting novel characteristics of autonomous parvovirus DNA replication. IMPORTANCEHuman bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1 capsid has been developed to efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to human airway epithelia. Here, we identified both cis-acting elements and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We localized the minimal replication origin, which contains both NS1 nicking and binding sites, to a 46-nucleotide sequence in the right-end hairpin. The identification of these essential elements of HBoV1 DNA replication acting both in cis and in trans will provide guidance to develop antiviral strategies targeting viral DNA replication at the right-end hairpin and to design next-generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases. Human bocavirus 1 (HBoV1) is a recently identified respiratory virus associated with acute respiratory tract infections in young children (1-9). HBoV1 belongs to the Bocaparvovirus genus within the Parvoviridae family (10, 11). Other species in the Bocaparvovirus genus include minute vi...

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“…These functions are known to include endonuclease and helicase activity [38]. Unlike Apoptin, NS1 has a partial X-ray crystal structure, which has demonstrated that the protein has a more distinct structure of alpha helices and beta sheets, making it the only protein discussed in this review with distinctly folded domains [39,40]. NS1 is also known to self-associate, although the exact size of these oligomers is still unclear [41,42].…”

Section: Ns1mentioning

confidence: 99%

Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

Wyatt

Müller

Tavassoli

2019

Cancers

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Cell death is a tightly regulated process which can be exploited in cancer treatment to drive the killing of the tumour. Several conventional cancer therapies including chemotherapeutic agents target pathways involved in cell death, yet they often fail due to the lack of selectivity they have for tumour cells over healthy cells. Over the past decade, research has demonstrated the existence of numerous proteins which have an intrinsic tumour-specific toxicity, several of which originate from viruses. These tumour-selective viral proteins, although from distinct backgrounds, have several similar and interesting properties. Though the mechanism(s) of action of these proteins are not fully understood, it is possible that they can manipulate several cell death modes in cancer exemplifying the intricate interplay between these pathways. This review will discuss our current knowledge on the topic and outstanding questions, as well as deliberate the potential for viral proteins to progress into the clinic as successful cancer therapeutics.

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

Cited by 15 publications

References 57 publications

Design and implementation of structural bioinformatics projects for biological sciences undergraduate students

Design and implementation of structural bioinformatics projects for biological sciences undergraduate students

Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome

Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

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