Berlin 2024 – scientific programme

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BP: Fachverband Biologische Physik

BP 22: Bacterial Biophysics II

BP 22.3: Talk

Wednesday, March 20, 2024, 15:30–15:45, H 0112

How Does a Riboswitch Differentiate Between Mg²⁺ and its experimental mimic Mn²⁺ for Specific Binding? — Kushal Singh and •Govardhan Reddy Patluri — Indian Institute of Science, Bangalore, India

Metalloriboswitches regulate metal ion homeostasis in bacteria. The aptamer domain of the Mn-sensing riboswitch (Mn-AD) binds to Mn²⁺ with high specificity in the presence of Mg²⁺. However, Mn²⁺ can substitute Mg²⁺ in the binding pockets of RNA structures and is exploited as an experimental probe. To understand the specificity of Mn-AD towards Mn²⁺ sensing in the presence of Mg²⁺, we used computer simulations and RNA models with different resolutions. We find that the specificity of the binding pocket for Mn²⁺ binding is driven by kinetics as Mn²⁺ loses a water molecule from its first solvation shell and transitions to an inner-shell interaction with a phosphate oxygen in the binding pocket relatively faster compared to Mg²⁺. The enhanced sampling simulations show that Mn²⁺ further consolidates its binding to the MB pocket via conformational rearrangements, facilitating hierarchical dehydration of the six water molecules from its solvation shell and transitions to inner-shell coordination. The free energy for Mn²⁺ to lose six water molecules for its solvation shell is downhill compared to Mg²⁺. These results provide insight into how bacteria use RNA to sense specific metal ions from a pool of biologically relevant metal ions to maintain homeostasis.

Keywords: RNA, Riboswitch, Matal Ions, Simulations