A viral peptide deformylase‐ribosome complex reveals mechanism of host gene expression control (558.2)

Abstract

All prokaryotic nascent chains must be co‐translationally deformylated to allow the further essential removal of the first methionine. This early nascent chain processing is ensured by peptide deformylases (PDFs), an enzyme shown to interact with ribosome at the exit tunnel. Recently, studies demonstrating in one hand the acquisition by different marine phages of modified version of bacterial PDF and in the other hand that also viral proteins undergo deformylation led to propose that phage PDFs could be important for viral fitness. Aside from this intriguing hypothesis, not much is known about these phage PDFs. Here, we show that most viral versions of the PDFs do not contain a C‐terminal extension previously proposed to be responsible of direct PDF binding to ribosome. Nonetheless, we show that the smallest identified phage PDF, a fully C‐terminally‐truncated PDF, is still able to bind directly to ribosome via a new dedicated ribosome‐binding domain, playing a master regulator function. Crosslinking experiments and combination of structural data of this phage PDF alone and the complex between the phage PDF and the ribosome show that the phage PDF interacts with ribosome in several distinct regions. Taking together, our findings provide basis for understanding of a previously unrecognized mechanism based on the pathogenic virus control of host viability at the level of the tunnel exit.Grant Funding Source: CNRS, ANR