Functional analysis of enzymes involved in the co-translational modification of nascent chains

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N-terminal processing of nascent polypeptides is an essential proteolytic pathway existing in all organisms. In bacteria, nascent chains are processed in two consecutive reactions. First, peptide deformylase (PDF) removes the N-terminal formyl group. Second, the N-terminal methionine is proteolytically removed by methionine aminopetidase (MAP), a reaction that depends on the nature of the penultimate amino acid. Eukaryotes lack N-terminal formylation and nascent chains are directly processed by MAPs, but most nascent chains are acetylated at their N-terminus by ribosome associated N-acetyltransferases (NATs). Enzymatic modifications occur in early phases of translation concomitantly with initial steps of protein folding or co-translational targeting of the growing polypeptide to the translocon. In order to maintain accuracy of this process, it must be highly coordinated. Our scientific aim is to analyze (i) the spatial and temporal coordination of PDF and MAP with further factors interacting with nascent chains (e.g. the chaperone trigger factor and the targeting factors SRP and SecA), (ii) the potential ribosome association of bacterial N-acetyltransferases and the adaptor prote in SspB, a protein involved in the recognition and degradation of SsrA-tagged proteins by the AAA+ protease ClpXP, and (iii) the importance of N-terminal processing and modification for folding and stability of newly synthesized proteins.