EMD-50200
EVA71 E096A native particle
EMD-50200
Single-particle2.5 Å
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Map released: 04/09/2024
Last modified: 02/10/2024
Sample Organism:
Enterovirus A71
Sample: Enterovirus A71
Fitted models: 9f5s (Avg. Q-score: 0.638)
Deposition Authors: Kingston NJ
,
Stonehouse NJ
,
Rowlands DJ
,
Hogle JM
,
Filman DJ
,
Snowden JSS
Sample: Enterovirus A71
Fitted models: 9f5s (Avg. Q-score: 0.638)
Deposition Authors: Kingston NJ
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Mechanism of enterovirus VP0 maturation cleavage based on the structure of a stabilised assembly intermediate.
Kingston NJ
,
Snowden JS
,
Grehan K
,
Hall PK
,
Hietanen EV
,
Passchier TC
,
Polyak SJ
,
Filman DJ
,
Hogle JM
,
Rowlands DJ
,
Stonehouse NJ
(2024) PLoS Pathog , 20 , e1012511 - e1012511
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(2024) PLoS Pathog , 20 , e1012511 - e1012511
Abstract:
Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0. We have demonstrated an essential role of VP0 E096 in VP0 cleavage independent of RNA encapsidation and generated a new model of capsid maturation, supported by bioinformatic analysis. This provides a molecular basis for RNA-dependence, where RNA induces conformational changes required for VP0 maturation, but that RNA packaging itself is not sufficient to induce maturation. These data have implications for understanding production of infectious virions and potential relevance for future vaccine and antiviral drug design.
Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0. We have demonstrated an essential role of VP0 E096 in VP0 cleavage independent of RNA encapsidation and generated a new model of capsid maturation, supported by bioinformatic analysis. This provides a molecular basis for RNA-dependence, where RNA induces conformational changes required for VP0 maturation, but that RNA packaging itself is not sufficient to induce maturation. These data have implications for understanding production of infectious virions and potential relevance for future vaccine and antiviral drug design.