FRIAS Colloquium - Yavuz Öztürk

A new class of regulatory sensor peptides for copper homeostasis

Metabolic sensing is a fundamental biological process for cells to adapt to changing environments. In bacteria, the response to metabolites is primarily controlled by transcriptional regulators, which activate or repress gene expression to ensure metabolic acclimation. Besides, ribosomal stalling during the translation can also contribute to cellular acclimation and has been shown to mediate responses to changing intracellular molecules. In the current study, we demonstrate that the cotranslational export of the Rhodobacter capsulatus protein CutF regulates the translation of the downstream multicopper oxidase CutO in response to extracellular copper (Cu). Our data show that CutF is cotranslationally exported by the signal recognition particle pathway and acts as a Cu sensor. The binding of Cu to the periplasmically exposed Cu-binding motif of CutF delays its cotranslational export via its C-terminal ribosome stalling motif. This allows for the unfolding of an mRNA stem-loop sequence that shields the ribosome binding site of cutO, which favors its subsequent translation. Bioinformatic analyses reveal that CutF-like proteins are widely distributed in bacteria and are often located upstream of genes involved in transition metal homeostasis. In summary, our data reveal a largely conserved translational control mechanism that allows to integration the concentration of extracellular nutrients into metabolic adaptation.