Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel


Kolar MH, Nagy G, Kunkel J, Vaiana SM, Bock LV, Grubmüller H




bioRxiv 2021.04.15.440051.


The ribosome is a fundamental biomolecular complex responsible for protein production in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiologic consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form an α-helix in the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP sequence has a low helical propensity in water and that the propensity is higher in more hydrophobic solvents. We propose that helix formation within the ribosome is driven by the tunnel environment and that a portion of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling the α-helix formation, which causes the elongation arrest.