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Ribosomes are complex biomachines responsible for protein synthesis in all organisms. The ribosome consists of three strands of RNA and dozens of ribosomal proteins. It is organized into two subunits, where the small subunit reads the mRNA and the large subunit catalyzes peptide bond formation. The nascent protein translocates from the catalytic center to the ribosome surface through a 10 nm-long exit tunnel.
Protein synthesis is a highly regulated process. We have hypothesized a long-distance allostery within the ribosome, which could bring information about the tunnel content to the ribosome surface. The anticipated allosteric path engages ribosomal protein uL22, one of two ribosomal proteins that span the large subunit from the surface deep into the exit tunnel. On the ribosome surface, uL22 binds the peptide deformylase (PDF), an enzyme which initiates protein maturation in bacteria by removing the formyl group from the leading methionine of the nascent protein.
We have used all-atom explicit-water molecular dynamics simulations in equilibrium and non-equilibrium regimes, and describe the effect of PDF binding on the structure and dynamics of uL22. PDF binds through its C-terminal alpha-helix. The binding induces a conformational change of uL22 loops, one located on the surface and another in the exit tunnel. Although the signal-to-noise ratio in the equilibrium simulations is modest, the non-equilibrium simulations suggest that the PDF binding also affects the flexibility of the uL22 loop exposed to the tunnel. This could hint that PDF binding might affect the rate of nascent chain translocation through the exit tunnel.
