Mycobacterium tuberculosis in the proteomics era

More than 60 years ago, Swedish biochemist Pehr Edman introduced the first technique for single peptide sequencing (1). The underlying principle involves a phenylisothiocyanate reaction with the free N-terminal amino group of a given peptide. The modified amino acid is then cleaved off and identified by chromatography or electrophoresis. Further cycles of the same process allow consecutive determination of up to 30 amino acids and thus the N-terminal amino acid sequence of a polypeptide. Major drawbacks of the so-called Edman degradation are that (i) N-terminal residues of a polypeptide must be freely accessible and unmodified and (ii) disulfide bonds cannot be directly identified. Nevertheless, Edman paved the way to modern protein identification. Proteomics has come a long way and is currently in transition from pure basic research to medical application. The reasons are obvious. The genome can be viewed as the blueprint of a cell; the transcriptome encompasses the first step, transcribing parts of the genome, which is active at a given time point. The proteome, however, describes the sum of the working parts of a cell. Thus, proteomics is the most direct platform for measuring cellular activity. Importantly, both during transcription from DNA to RNA and during translation from RNA to protein, changes occur, which can multiply the different variants of the encoding gene. These include transcription errors, epigenetic changes, and other events, as well as translation errors, posttranslational modifications such as phosphorylation, and differential modes of protein folding. These changes increase complexity markedly, thereby allowing the most direct and most precise insight into a cell.