6THD

Multiple Genomic RNA-Coat Protein Contacts Play Vital Roles in the Assembly of Infectious Enterovirus-E

Summary for 6THD

• Entry DOI: 10.2210/pdb6thd/pdb
• EMDB information: 10504
• Descriptor: Genome polyprotein, MYRISTIC ACID, SULFATE ION, ... (7 entities in total)
• Functional Keywords: bev1, enterovirus, picornavirus, rna, virus
• Biological source: Bovine enterovirus (strain VG-5-27); More
• Total number of polymer chains: 4
• Total formula weight: 91501.75

Authors

Chandler-Bostock, R.,Mata, C.P.,Bingham, R.,Dykeman, E.J.,Meng, B.,Tuthill, T.J.,Rowlands, D.J.,Ranson, N.A.,Twarock, R.,Stockley, P.G. (deposition date: 2019-11-19, release date: 2020-12-09, Last modification date: 2024-05-22)

Primary citation

Chandler-Bostock, R.,Mata, C.P.,Bingham, R.J.,Dykeman, E.C.,Meng, B.,Tuthill, T.J.,Rowlands, D.J.,Ranson, N.A.,Twarock, R.,Stockley, P.G.
Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts.
Plos Pathog., 16:e1009146-e1009146, 2020

PubMed Abstract: Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses.

PubMed: 33370422
DOI: 10.1371/journal.ppat.1009146

Experimental method

ELECTRON MICROSCOPY (2.23 Å)