Targeting Sequences

This chapter reveals that the targeting sequences direct proteins to the correct cellular compartment. Protein secretion in eukaryotic, bacterial, and archaeal cells depends on N-terminal signal peptides. The signal peptide is usually cleaved off by a signal peptidase, although some proteins have noncleaved signal peptides. Tat signal peptides are not recognized by the SRP or other components of the Sec machinery. Most soluble matrix proteins have N-terminal mitochondrial targeting peptides that are removed by a matrix-localized protease upon import. Sequence analysis, mutational studies, and structure determination by nuclear magnetic resonance (NMR) have shown that an ability to form a positively charged, amphiphilic-helix is critical for the import function, as seen most clearly in the recently determined structure of a targeting peptide bound to a domain of the outer membrane receptor Tom20. Many intermembrane space proteins have bipartite targeting signals, where a typical matrix-targeting peptide is followed by a second targeting peptide with similarities to Sec-type signal peptides. Once imported into the stroma, some chloroplast proteins need to be further sorted to the lumen of the thylakoids. Overall this chapter reviews the main classes of “primary” targeting signals—secretory signal peptides, nuclear localization signals, mitochondrial targeting peptides, peroxisomal targeting sequences, and chloroplast transit peptides.