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TitleConserved structures and dynamics in 5'-proximal regions of Betacoronavirus RNA genomes.
Journal, issue, pagesNucleic Acids Res, Vol. 52, Issue 6, Page 3419-3432, Year 2024
Publish dateApr 12, 2024
AuthorsTales Rocha de Moura / Elżbieta Purta / Agata Bernat / Eva M Martín-Cuevas / Małgorzata Kurkowska / Eugene F Baulin / Sunandan Mukherjee / Jakub Nowak / Artur P Biela / Michał Rawski / Sebastian Glatt / Fernando Moreno-Herrero / Janusz M Bujnicki /
PubMed AbstractBetacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the ...Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular diversity. The development of novel antivirals hinges on understanding the key regulatory elements within the viral RNA genomes, in particular the 5'-proximal region, which is pivotal for viral protein synthesis. Using a combination of cryo-electron microscopy, atomic force microscopy, chemical probing, and computational modeling, we determined the structures of 5'-proximal regions in RNA genomes of Betacoronaviruses from four subgenera: OC43-CoV, SARS-CoV-2, MERS-CoV, and Rousettus bat-CoV. We obtained cryo-electron microscopy maps and determined atomic-resolution models for the stem-loop-5 (SL5) region at the translation start site and found that despite low sequence similarity and variable length of the helical elements it exhibits a remarkable structural conservation. Atomic force microscopy imaging revealed a common domain organization and a dynamic arrangement of structural elements connected with flexible linkers across all four Betacoronavirus subgenera. Together, these results reveal common features of a critical regulatory region shared between different Betacoronavirus RNA genomes, which may allow targeting of these RNAs by broad-spectrum antiviral therapeutics.
External linksNucleic Acids Res / PubMed:38426934 / PubMed Central
MethodsEM (single particle)
Resolution5.9 - 7.1 Å
Structure data

18520

8qo2

EMDB-18520, PDB-8qo2:
Conserved Structures and Dynamics in 5-Proximal Regions of Betacoronavirus RNA Genomes
Method: EM (single particle) / Resolution: 7.1 Å

18521

8qo3

EMDB-18521, PDB-8qo3:
Conserved Structures and Dynamics in 5-Proximal Regions of Betacoronavirus RNA Genomes
Method: EM (single particle) / Resolution: 6.6 Å

18522

8qo4

EMDB-18522, PDB-8qo4:
Conserved Structures and Dynamics in 5-Proximal Regions of Betacoronavirus RNA Genomes
Method: EM (single particle) / Resolution: 5.9 Å

18523

8qo5

EMDB-18523, PDB-8qo5:
Conserved Structures and Dynamics in 5-Proximal Regions of Betacoronavirus RNA Genomes
Method: EM (single particle) / Resolution: 6.5 Å

Source
  • human coronavirus oc43
  • rousettus bat coronavirus gccdc1
  • middle east respiratory syndrome-related coronavirus
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRUS / RNA structure / 5-proximal region / Coronavirus / Cryo-EM

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