Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution

Basavappa, Ravi; Syed, Rashid; Flore, Ornella; Icenogle, Joseph P.; Filman, David J.; Hogle, James M.

doi:10.1002/pro.5560031005

Cited by 186 publications

(247 citation statements)

References 52 publications

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Section: Introductionmentioning

confidence: 99%

“…I). Concomitantly with RNA encapsidation, VPO is cleaved to VP4 and VP2; it is believed that the RNA itself exerts a catalytic function in this event (Arnold et a!., 1987;Harber et al, 1991;Bishop &Anderson, 1993;Basavappa et al, 1994).In addition to processing of the viral polyprotein, the proteinases also cleave cellular targets. When infected with poliovirus, at least nine acidic and five basic cellular proteins were shown to be degraded in two-dimensional gel electrophoresis (Urzanqui & Carrasco, 1989).…”

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confidence: 99%

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Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

et al. 1996

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Picornaviral proteinases are responsible for maturation cleavages of the viral polyprotein, but also catalyze the degradation of cellular targets. Using graphical visualization techniques and neural network algorithms, we have investigated the sequence specificity of the two proteinases 2AP" and 3CPm. The cleavage of VPO (giving rise to VP2 and VP4). which is carried out by a so-far unknown proteinase, was also examined. In combination with a novel surface exposure prediction algorithm, our neural network approach successfully distinguishes known cleavage sites from noncleavage sites and yields a more consistent definition of features common to these sites. The method is able to predict experimentally determined cleavage sites in cellular proteins. We present a list of mammalian and other proteins that are predicted to be possible targets for the viral proteinases. Whether these proteins are indeed cleaved awaits experimental verification. Additionally, we report several errors detected in the protein databases.A computer server for prediction of cleavage sites by picornaviral proteinases is publicly available at the e-mail address NetPicoRNA@cbs.dtu.dk or via WWW at http://www.cbs.dtu.dkfservices/NetPicoRNA.Keywords: cleavage site prediction; neural networks; picornavirus; proteinase; surface exposureMembers of the picornavirus family express their genomic RNA as a single polyprotein that is proteolytically processed to the mature polypeptides. At least three proteinases are required for the individual protein components to be released (reviewed in Krausslich Hellen et al., 1989;Lawson & Semler, 1990). The primary cleavage, which severs the capsid precursor PI from the nonstructural region P2-P3, is performed cotranslationally by the viral proteinase 2APm in enteroviruses and human rhinoviruses (HRVs; see Fig. I). Most of the remaining cleavages are catalyzed by the viral proteinase, 3CP". In cardio-, hepato-, and aphthoviruses, which also belong to the picornavirus family, the L-proteinase performs functions similar to those of 2APm, resulting in a somewhat different cleavage scheme (see Fig. I). Concomitantly with RNA encapsidation, VPO is cleaved to VP4 and VP2; it is believed that the RNA itself exerts a catalytic function in this event (Arnold et a!., 1987;Harber et al., 1991;Bishop &Anderson, 1993;Basavappa et al., 1994).In addition to processing of the viral polyprotein, the proteinases also cleave cellular targets. When infected with poliovirus, at least nine acidic and five basic cellular proteins were shown to be degraded in two-dimensional gel electrophoresis (Urzanqui & Carrasco, 1989). The degradation of cellular proteins seems to be part of the viral attack mechanism, leading to host cell shur-ofJ-a decrease in cellular transcription and translation that has no influence on viral replication. The best-studied event is the cleavage of the eukaryotic initiation factor 4G (eIF-4G). which is required for cap-dependent translation of cellular mRNA. This protein is degraded by 2APm in entero-and...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

et al. 1996

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“…Although empty particles are not thought to be direct precursors of mature virions, they may function as reservoirs of capsid components (11)(12)(13). For poliovirus, empty particles are unstable, readily converting from D-type native antigenicity to a state with altered antigenic properties (C-type) (9,14,15). EV71 cultured for vaccine development produces both full virions and empty particles, and the content of empty particles is at least 2-fold more than the full virion in the final production yield (16).…”

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confidence: 99%

Crystal Structures of Enterovirus 71 (EV71) Recombinant Virus Particles Provide Insights into Vaccine Design

Lyu

Wang

et al. 2015

Journal of Biological Chemistry

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Background:No HFMD vaccine is available. Results: Structures of EV71 recombinant virus particles were determined showing that the inserted foreign peptide is exposed on the particle surface without capsid structural changes and that virus uncoating is not affected. Conclusion: VP1 BC loop is suitable for foreign peptide insertion for the generation of recombinant EV71 viruses. Significance: The results provide insights into vaccine development.

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“…These changes are of particular interest in view of the inhibition of viral uncoating by WIN compounds. Cell attachment and uncoating to release viral RNA are associated with large conformational transitions in the capsid that transform the overall structure of the particle (25) and perturb interactions at the 5-fold axis (26,27). In addition to release of viral RNA, the N termini of VP1 and VP4 are externalized from their internal location in the capsid core.…”

Section: Discussionmentioning

confidence: 99%

Dissociation of an antiviral compound from the internal pocket of human rhinovirus 14 capsid

Zhou

Post

2005

Proc. Natl. Acad. Sci. U.S.A.

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WIN antiviral compounds bind human rhinovirus, as well as enterovirus and parechovirus, in an internal cavity located within the viral protein capsid. Access to the buried pocket necessitates deviation from the average viral protein structure identified by crystallography. We investigated the dissociation of WIN 52084 from the pocket in human rhinovirus 14 by using an adiabatic, biased molecular dynamics simulation method. Multiple dissociation trajectories are used to characterize the pathway. WIN 52084 exits between the polypeptide chain near the ends of ␤C and ␤H in a series of steps. Small, transient packing defects in the protein are sufficient for dissociation. A number of torsion-angle transitions of the antiviral compound are involved, which suggests that flexibility in antiviral compounds is important for binding. It is interesting to note that dissociation is associated with an increase in the conformational fluctuations of residues never in direct contact with WIN 52084 over the course of dissociation. These residues are N-terminal residues in the viral proteins VP3 and VP4 and are located in the interior of the capsid near the icosahedral 5-fold axis. The observed changes in dynamics may be relevant to structural changes associated with virion uncoating and its inhibition by antiviral compounds.antiviral activity ͉ antiviral binding ͉ ligand binding effects ͉ protein molecular dynamics ͉ picornavirus

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Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution

Cited by 186 publications

References 52 publications

Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

Crystal Structures of Enterovirus 71 (EV71) Recombinant Virus Particles Provide Insights into Vaccine Design

Dissociation of an antiviral compound from the internal pocket of human rhinovirus 14 capsid

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