In order to become folded and bioactive, proteins must be translated and protected from deleterious aggregation. This need is particularly compelling during and immediately after protein biosynthesis. Remarkably, the ribosome and molecular chaperones play a key role in this process. Here, we employed a combination of single-particle cryo-EM, time-resolved fluorescence-anisotropy decays, and other biophysical techniques to analyze protein-protein and protein-chaperone interactions experienced by nascent chains before and immediately after release from the ribosome. We found that, in the absence of molecular chaperones, ribosome-bound nascent chains (RNCs) interact with the L23 ribosomal protein (r-protein) and with other r-proteins located within the outer surface and vestibule of the ribosome. The scenario changes in the presence of chaperones, revealing a peculiar interplay between RNC conformational sampling and interactions with ribosomal surface and (or) chaperones during the early stages of protein life. Implications of the above findings for basic science and biotechnology, including the efficient overproduction of pharmaceuticals in bacteria and the design of novel antibacterial strategies, will be discussed.
Cavagnero et al. (Sun,) studied this question.