126 results found
Holbrook JB, Curry S, Kamerlin SCL, 2018, Debate on academic freedom and open access is healthy., Publisher: Nature Research
Hatch A, Curry S, 2018, Evaluation woes: We're on it, responds DORA
Curry S, 2018, Let’s move beyond the rhetoric: it’s time to change how we judge research, Nature, Vol: 554, Pages: 147-147
Li T-F, Hosmillo M, Schwanke H, et al., 2017, Human Norovirus NS3 has RNA Helicase and Chaperoning Activities., Journal of Virology, Vol: 92, ISSN: 1098-5514
RNA remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions, and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-stranded RNA viruses in the family Caliciviridae, and constitute a significant and potentially fatal threat to human health. Here we report that protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA chaperoning activity that can remodel structured RNAs and facilitate strand-annealing. Moreover, NS3 can facilitate viral RNA synthesis in vitro by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound and, more importantly, that it reduces the replication of norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA remodeling activities encoded by Caliciviridae, and highlight the functional significance of NS3 in noroviral life cycle.IMPORTANCE Noroviruses are a diverse group of positive-stranded RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to associate with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein NS3 not only has ATP-dependent helicase activity, but also acts as an ATP-in
Newman J, Asfor AS, Berryman S, et al., 2017, The cellular chaperone heat shock protein 90 is required for foot-and-mouth disease virus capsid precursor processing and assembly of capsid pentamers, Journal of Virology, Vol: 92, ISSN: 1098-5514
Productive picornavirus infection requires the hijack of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerisation of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and post-translational modification of the capsid precursor (P1-2A) by viral and cellular enzymes, and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90), impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titre by more than ten-fold while not affecting the activity of a sub-genomic replicon indicating that translation and replication of viral RNA were unaffected by the drug.
Curry S, 2017, Guest Editorial: Open Access: Principles, Practice, and Potential, Publisher: AMER CHEMICAL SOC
In 2013, the UK Arts and Humanities Research Council funded a 4-year project onthe editorial and commercial history of the world’s oldest-surviving scholarly journal(‘Publishing the Philosophical Transactions: a social, cultural and economic history ofa learned journal, 1665-2015’, AH/K001841). The project is led by Dr Aileen Fyfe at theUniversity of St Andrews in partnership with the Royal Society.The project team convened a workshop at the Royal Society, 22 April 2016, on ‘The Politicsof Academic Publishing, 1950-2016’. This briefing paper is informed by the contributionsof those who attended that day, and we thank them for their insights. The authors of thisbriefing paper are a sub-group of those who attended the April 2016 workshop.This report is based upon the primary (historical) research of the PhilosophicalTransactions project team, combined with a literature review, and the expertise of the otherauthors (principally in higher education research, and in scholarly communication).
Curry S, Rohn J, Steele A, 2016, UK research reform: protest now, Publisher: NATURE PUBLISHING GROUP
Lariviere V, Kiermer V, MacCallum CJ, et al., 2016, A simple proposal for the publication of journal citation distributions, Publisher: bioRxiv
Although the Journal Impact Factor (JIF) is widely acknowledged to be a poor indicator of the quality of individual papers, it is used routinely to evaluate research and researchers. Here, we present a simple method for generating the citation distributions that underlie JIFs. Application of this straightforward protocol reveals the full extent of the skew of these distributions and the variation in citations received by published papers that is characteristic of all scientific journals. Although there are differences among journals across the spectrum of JIFs, the citation distributions overlap extensively, demonstrating that the citation performance of individual papers cannot be inferred from the JIF. We propose that this methodology be adopted by all journals as a move to greater transparency, one that should help to refocus attention on individual pieces of work and counter the inappropriate usage of JIFs during the process of research assessment.
Curry S, 2016, What is the meaning of Brexit?, EMBO Reports, Vol: 17, Pages: 1239-1240, ISSN: 1469-221X
Yang J, Leen EN, Maree FF, et al., 2016, Crystal structure of the 3C protease from Southern African Territories type foot-and-mouth disease virus 2, PEERJ, Vol: 4, ISSN: 2167-8359
Curry S, 2016, Perspectives: It's time for positive action on negative results, Chemical and Engineering News, Vol: 94, Pages: 34-35, ISSN: 0009-2347
Hosmillo M, Sweeney TR, Chaudhry Y, et al., 2016, The RNA Helicase eIF4A Is Required for Sapovirus Translation, Journal of Virology, Vol: 90, Pages: 5200-5204, ISSN: 1098-5514
The eukaryotic initiation factor 4A (eIF4A) is a DEAD box helicase that unwinds RNA structure in the 5′ untranslated region (UTR) of mRNAs. Here, we investigated the role of eIF4A in porcine sapovirus VPg-dependent translation. Using inhibitors and dominant-negative mutants, we found that eIF4A is required for viral translation and infectivity, suggesting that despite the presence of a very short 5′ UTR, eIF4A is required to unwind RNA structure in the sapovirus genome to facilitate virus translation.
Yang J, Leen EN, Maree FF, et al., 2016, Crystal structure of the 3C protease from South African Territories type 2 foot-and-mouth disease virus, Publisher: PeerJ Preprints
The replication of foot-and-mouth disease virus (FMDV) is dependent on the virus-encoded 3C protease (3Cpro). As in other picornaviruses, 3Cpro performs most of the proteolytic processing of the polyprotein expressed from the single open reading frame in the RNA genome of the virus. Previous work revealed that the 3Cpro from serotype A – one of the seven serotypes of FMDV – adopts a trypsin-like fold. Phylogenetically the FMDV serotypes are grouped into two clusters, with O, A, C, and Asia 1 in one, and the three South African Territories serotypes, (SAT-1, SAT-2 and SAT-3) in another. We report here the cloning, expression and purification of 3C proteases from four SAT serotype viruses (SAT2/GHA/8/91, SAT1/NIG/5/81, SAT1/UGA/1/97, and SAT2/ZIM/7/83) and the crystal structure at 3.2 Å resolution of 3Cpro from SAT2/GHA/8/91).
Leen EN, Sorgeloos F, Correia S, et al., 2016, A Conserved Interaction between a C-Terminal Motif in Norovirus VPg and the HEAT-1 Domain of eIF4G Is Essential for Translation Initiation., PLOS Pathogens, Vol: 12, ISSN: 1553-7366
Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5´ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5´-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652-1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.
Curry S, 2015, Structural biology: a century-long journey into an unseen world, Interdisciplinary Science Reviews, Vol: 40, Pages: 308-328, ISSN: 0308-0188
Curry S, Leen EN, Sorgeloos F, et al., 2015, A conserved interaction between a C-terminal motif in Norovirus VPg and the HEAT-1 domain of eIF4G is essential for translation initiation, Publisher: bioRxiv
Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5 ́ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5 ́-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652-1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C-terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C- terminal peptide of MNV VPg to inhibit translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.
Fernandes H, Leen EN, Cromwell H, et al., 2015, Structure determination of Murine Norovirus NS6 proteases with C-terminal extensions designed to probe protease-substrate interactions, PEERJ, Vol: 3, ISSN: 2167-8359
Curry S, 2015, The power of preprint, Biologist, Vol: 62, ISSN: 0006-3347
Chung L, Bailey D, Leen EN, et al., 2014, Norovirus Translation Requires an Interaction between the C Terminus of the Genome-linked Viral Protein VPg and Eukaryotic Translation Initiation Factor 4G, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 21738-21750
Curry S, 2014, Open access - reasons to be cheerful: a reply to Agrawal, Trends in Plant Science, Vol: 19, Pages: 196-197
Anurag Agrawal's recent letter on open access publishing raises an important topic that many researchers may have found difficult to engage with, not least because its myriad complexities are frequently enveloped in strong cross-currents of opinion. Agrawal is concerned that some scientists might still be rather uncritical of the accelerating open-access bandwagon and rightly highlights some of the possible pitfalls. However, although it is important to be aware of the risks of open access, Agrawal was more pessimistic in his assessment than is warranted by the evidence and, in my view, paid insufficient attention to the possible benefits.
Joshi A, Esteve V, Buckroyd AN, et al., 2014, Solution and crystal structures of a C-terminal fragment of the neuronal isoform of the polypyrimidine tract binding protein (nPTB), PEERJ, Vol: 2, ISSN: 2167-8359
Roqué Rosell NR, Mokhlesi L, Milton NE, et al., 2014, Design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3C protease., Bioorg Med Chem Lett, Vol: 24, Pages: 490-494
Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3C protease, making this enzyme an attractive target for antiviral drugs. A peptide corresponding to an optimal substrate has been modified at the C-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as Michael acceptors with the enzyme active site. Further investigation highlighted key structural determinants for inhibition, with a positively charged P2 being particularly important for potency.
Mickleburgh I, Kafasla P, Cherny D, et al., 2014, The organization of RNA contacts by PTB for regulation of FAS splicing, NUCLEIC ACIDS RESEARCH, Vol: 42, Pages: 8605-8620, ISSN: 0305-1048
Zhou Z, Mogensen MM, Powell PP, et al., 2013, Foot-and-Mouth Disease Virus 3C Protease Induces Fragmentation of the Golgi Compartment and Blocks Intra-Golgi Transport, JOURNAL OF VIROLOGY, Vol: 87, Pages: 11721-11729, ISSN: 0022-538X
Leen EN, Kwok KYR, Birtley JR, et al., 2013, Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg Proteins, JOURNAL OF VIROLOGY, Vol: 87, Pages: 5318-5330, ISSN: 0022-538X
Curry S, 2013, Open access: brave new world requires bravery, Insights, Vol: 26, Pages: 22-27, ISSN: 2048-7754
Porta C, Xu X, Loureiro S, et al., 2013, Efficient production of foot-and-mouth disease virus empty capsids in insect cells following down regulation of 3C protease activity, JOURNAL OF VIROLOGICAL METHODS, Vol: 187, Pages: 406-412, ISSN: 0166-0934
Curry S, 2012, Access all areas, NEW SCIENTIST, Vol: 214, Pages: 26-27, ISSN: 0262-4079
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.