Abstract
Under the oxidative stress condition, the small RNA (sRNA) OxyS that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in the defection of gene regulation. However, how the Hfq protein interacts with sRNA OxyS and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result was correlated with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly came from the increased van der Waals interactions (vdW). This research explored the binding mechanism between Oxys and chaperone protein Hfq and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights into the mechanism of gene expression regulation affected by protein mutations.
Highlights
Academic Editors: Zhiliang Ji, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai
The small RNA which cannot be encoded into protein owing to the absence of open reading frames plays a critical role in the regulation of gene expression [1,2,3,4]
The root means square deviation (RMSD) of the backbone atoms in Hfq and OxyS small RNA (sRNA) relative to the initial structure for all systems were calculated to ensure that the systems had reached equilibrium during the simulation (Figures S1–S4)
Summary
Academic Editors: Zhiliang Ji, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai. The small RNA (sRNA) which cannot be encoded into protein owing to the absence of open reading frames plays a critical role in the regulation of gene expression [1,2,3,4] Under environmental stresses such as oxidative stress, low temperature, iron ion concentration, and so on, different types of sRNA are produced to regulate the expression of genes by targeting different messenger RNA (mRNA) and affecting their structures as well as translation efficiency [5,6,7]. In this process, the target mRNA can encode proteins in response to external changes and hostile environments. The latter, referred to as trans-encoded sRNA orchestrate dynamics response, most strongly depend on the RNA chaperone Hfq that published maps and institutional affiliations
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