Unveiling Putative Excited State and Transmission of Binding Information in the Fluoride Riboswitch

Riboswitches regulate downstream
gene expression by binding to
specific small molecules or ions with multiple mechanisms to transfer
the binding information. In the case of the fluoride riboswitch, the
transcription termination signal is conveyed through a transient excited
state (ES). In this work, we performed conventional molecular dynamics
(MD) simulations, totaling 180 μs, to obtain the ES structure
and investigate the mechanism underlying information transmission
in Mg2+/F– binding within the fluoride
riboswitch aptamer. The Mg2+/F– binding
pocket exhibits various conformations in its apo form. A series of
ES structures were extracted from the MD trajectories of the apo form.
The dynamics of the Mg2+/F– binding pocket
influenced key pair A40–U48 in ES structures. The pathway connecting
the binding pocket to the pair involves interactions between the phosphate
groups of U7 and G8 and the nucleobases of G8–C47–U48.
Our work presents a structural ensemble of the ES and elucidates a
pathway for transferring Mg2+/F– binding
information, thereby facilitating the understanding of how the holo-like
apo state achieves transcriptional repression.