Mutations of N1 Riboswitch Affect its Dynamics and Recognition by Neomycin Through Conformational Selection.

ABSTRACT: Short, structured fragments of non-coding mRNA may act as molecular switches upon binding specific ligands, regulating the translation of proteins encoded downstream this mRNA sequence. One switch, called riboswitch N1, is regulated by aminoglycosides such as neomycin. Nucleobase mutations in the apical loop, although distant from the binding pocket, significantly affect neomycin affinity and riboswitch regulatory efficiency. To explain this influence, we conducted molecular dynamics simulations using generalized replica exchange with solute tempering (gREST). Translation assay of a reporter protein in a yeast system shows that mutating A17 to G in the riboswitch apical loop reduces 6-fold the translation regulation efficiency of the mutant. Indeed, simulations of the unbound riboswitch sh

SUBMITTER: Chyzy P 

PROVIDER: S-EPMC7942488 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature