8QO3

Conserved Structures and Dynamics in 5-Proximal Regions of Betacoronavirus RNA Genomes

Summary for 8QO3

• Entry DOI: 10.2210/pdb8qo3/pdb
• EMDB information: 18521
• Descriptor: RoBat-CoV-SL5 (1 entity in total)
• Functional Keywords: rna structure, 5-proximal region, coronavirus, cryo-em, virus
• Biological source: Rousettus bat coronavirus GCCDC1
• Total number of polymer chains: 1
• Total formula weight: 37739.09

Authors

Moura, T.R.,Purta, E.,Bernat, A.,Baulin, E.,Mukherjee, S.,Bujnicki, J.M. (deposition date: 2023-09-28, release date: 2024-03-06, Last modification date: 2024-04-24)

Primary citation

de Moura, T.R.,Purta, E.,Bernat, A.,Martin-Cuevas, E.M.,Kurkowska, M.,Baulin, E.F.,Mukherjee, S.,Nowak, J.,Biela, A.P.,Rawski, M.,Glatt, S.,Moreno-Herrero, F.,Bujnicki, J.M.
Conserved structures and dynamics in 5'-proximal regions of Betacoronavirus RNA genomes.
Nucleic Acids Res., 52:3419-3432, 2024

PubMed Abstract: 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.

PubMed: 38426934
DOI: 10.1093/nar/gkae144

Experimental method

ELECTRON MICROSCOPY (6.6 Å)