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

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 n

SUBMITTER: Neupane K 

PROVIDER: S-EPMC8346527 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature