Recognition and Binding of RsmE to an AGGAC Motif of RsmZ: Insights from Molecular Dynamics Simulations

ORMAZÁBAL, AGUSTÍN; PIERDOMINICI-SOTTILE, GUSTAVO; PALMA, JULIANA

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Año: 2022

1549-9596

CsrA/RsmE is a post-transcriptional regulator protein widely distributed in bacteria. It impedes the expression of target mRNAs by attaching their 5´ untranslated region. The translation is restored by small, non-coding RNAs that sequester CsrA/RsmE acting as sponges. In both cases, the protein recognizes and attaches to specific AGGAX and AXGGAX motifs, where X refers to any nucleotide. RsmZ of {it Pseudomonas protegens} is one of these small RNAs. The structures of some of its complexes with RsmE were disclosed a few years ago. We have used Umbrella Sampling simulations to force the unbinding of RsmE from the AGGAC motif located in the single-stranded region sited between stem-loops 2 and 3 of RsmZ. The calculations unveiled the identity of the main residues and nucleotides involved in the process. They also showed that the region adopts a hairpin-like conformation during the initial stages of the binding. The ability to acquire this conformation requires that the region has a length of, at least, nine nucleotides. Besides, we performed standard Molecular Dynamics simulations of the isolated fragments, analyzed their typical conformations, and characterized their movements. This analysis revealed that the free molecules oscillate along specific collective coordinates that facilitate the initial stages of the binding. The results strongly suggest that the flexibility of the single-stranded region of RsmZ crucially affects the ability of its binding motif to catch RsmE.