לוח שנה משולב

In this contribution, NMR and other integrated structural biology studies will be presented that investigate the role of coding and non-coding mRNAs in guiding protein translation.
First, we will discuss how the choice of mRNA-codons can impact protein folding. In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins.
Second, we investigate the coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains. Thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.
Third, we present our work on non-coding translational riboswitches are cis-acting RNA regulators that modulate the of genes during translation initiation. Our investigation thus unravels the intricate dynamic network involving RNA regulator, ligand inducer and ribosome protein modulator during translation initiation.