On the Effect of the Ribosome and Trigger Factor on Nascent Chain Protein Folding

Abstract

It has been established that nascent proteins can fold concomitant with their synthesis on the ribosome and that chaperones such as Trigger Factor (TF) can interact with the growing nascent chain. The impact of the ribosome and TF on protein folding properties is still largely unknown, although recent studies suggest that in the near future high resolution information on contranslational folding will be available. Motivated by this, and with the goal of outlining plausible folding scenarios in vivo, we use coarse-grained simulations to examine folding in the presence and absence of the ribosome and TF. Using physically plausible interaction strengths between TF and the ribosome, parameterized based on experimental binding free energies, we have used replica exchange simulations to explore the impact of these in vivo actors on nascent chain folding. We find the ribosome significantly perturbs most protein folding properties, altering the distribution of folding pathways and favoring N-terminal folding of the nascent protein domain, suggesting that new scenarios of folding can occur on the ribosome. We then explore how TF alters cotranslational folding properties and discuss these findings in the context of recent NMR results.View Large Image | View Hi-Res Image | Download PowerPoint Slide