Molecular Dynamics Simulations Unveil the Basis of the Sequential Binding of RsmE to the Noncoding RNA RsmZ

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

JOURNAL OF PHYSICAL CHEMISTRY B - (Print)

AMER CHEMICAL SOC

Año: 2021

1520-6106

CsrA/RsmE are dimeric proteins that bind to targeted mRNAs repressing translation. This mechanism modulates several metabolic pathways and allows bacteria to efficiently adjust their responses to environmental changes. In turn, small RNAs (sRNA) such as CsrB or RsmZ, restore translation by sequestering CsrA/RsmE dimers. Thus, these molecules act in tandem as a gene-expression regulatory system. Recently, a combined NMR-EPR approach solved the structure of part of RsmZ of Pseudomonas fluorescens, attached to three RsmE dimers. The study demonstrated that RsmE assembles onto RsmZ following a specific sequential order. The reasons underlying this peculiar behavior are still unclear. Here, we present a Molecular Dynamics analysis that explores the conformational diversity of RsmZ and RsmZ-RsmE complexes. The results reveal a clear pattern regarding the exposure of the alternative GGA binding motifs of RsmZ. This pattern is tuned by the attachment of RsmE dimers. Altogether, the observations provide a simple and convincing explanation for the order observed in the sequestration of RsmE dimers. Typical structures for RsmZ and RsmZ-RsmE complexes have been identified. Their characteristics concerning the exposure of the GGA sequences are presented and their most significant interactions are described.