Newton's cradle-like allosteric mechanism explains regulatory RsmE RNA binding.

In the bacterial Csr/Rsm system, non-coding RNAs activate mRNA translation by removing homodimeric Csr/Rsm proteins from ribosome-binding sites of mRNAs. In Pseudomonas protegens, each RsmZ ncRNA sequesters up to five RsmE dimers sequentially and specifically within a narrow affinity range, functioning as a 'protein sponge'. Although the RsmE binding cascade is cooperative, binding of the highest affinity stem-loop RNA in RsmZ (SL2) reduces RNA binding affinity at the second site 10- to 30-fold. This unusual negative cooperativity may facilitate RsmE release from tightly bound mRNA for handover to the non-coding RNA, yet the underlying mechanisms remain unclear. Using Isothermal Titration Calorimetry, NMR spectroscopy and Molecular Dynamics, we reveal an allosteric mechanism resembling a Newton's cradle, coupling the binding at one site to conformational and dynamic changes at the second site, explaining the reduced affinity of the second binding event, and handover of RsmE dimer from mRNA to the ncRNA RsmZ.