Structural dynamics of single SARS-CoV-2 pseudoknot molecules reveal topologically distinct conformers

Krishna Neupane, Meng Zhao, Aaron Lyons, Sneha Munshi, Sandaru M. Ileperuma, Dustin B. Ritchie, Noel Q. Hoffer, Abhishek Narayan and Michael T. Woodside ()
Additional contact information
Krishna Neupane: University of Alberta
Meng Zhao: University of Alberta
Aaron Lyons: University of Alberta
Sneha Munshi: University of Alberta
Sandaru M. Ileperuma: University of Alberta
Dustin B. Ritchie: University of Alberta
Noel Q. Hoffer: University of Alberta
Abhishek Narayan: University of Alberta
Michael T. Woodside: University of Alberta

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract The RNA pseudoknot that stimulates programmed ribosomal frameshifting in SARS-CoV-2 is a possible drug target. To understand how it responds to mechanical tension applied by ribosomes, thought to play a key role during frameshifting, we probe its structural dynamics using optical tweezers. We find that it forms multiple structures: two pseudoknotted conformers with different stability and barriers, and alternative stem-loop structures. The pseudoknotted conformers have distinct topologies, one threading the 5′ end through a 3-helix junction to create a knot-like fold, the other with unthreaded 5′ end, consistent with structures observed via cryo-EM and simulations. Refolding of the pseudoknotted conformers starts with stem 1, followed by stem 3 and lastly stem 2; Mg2+ ions are not required, but increase pseudoknot mechanical rigidity and favor formation of the knot-like conformer. These results resolve the SARS-CoV-2 frameshift signal folding mechanism and highlight its conformational heterogeneity, with important implications for structure-based drug-discovery efforts.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25085-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25085-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25085-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().