Specific protein transport processes are essential to sequester proteins within membrane bound compartments or to export them effectively from cells. Such transport processes are commonly initiated by the interaction of characteristic targeting signals encoded in the primary sequence of proteins and their cognate receptor proteins, which mediate the interaction with the respective general transport machinery across the organellar, ER or bacterial membrane. Targeting signals for mitochondria (presequences), chloroplasts (transit peptides), peroxisomes (type-2 peroxisomal targeting signal, PTS2), but also for the ER (signal peptides) or the bacterial secretion system (signal peptides or signal sequences) share positions at the N-terminal part of the proteins and a characteristic alpha-helical sequence element. A high selectivity of the receptor proteins for different types of targeting signals is a prerequisite for specific protein transport. However, a detailed understanding of the width of diverse physiological functions associated with N-terminal targeting signals is only beginning to develop, which would certainly also benefit from a systematic comparison with other types of targeting signals, including those found internally and at the C-termini of polypeptides.
This Research Topic should broaden the understanding of the nature of N-terminal targeting signals and their diverse physiological roles by bringing together results from systematic analyses, novel biophysical methods and comparative bioinformatics analyses. By this means, the inherent differences between these targeting signals and the specificity of their recognition by receptor proteins should be emphasized. Recent results demonstrated a bilocalization of various mitochondrial and chloroplastic proteins suggesting a lower specificity of transport than anticipated. Moreover, differences in the characteristics of signal peptides mediating co- or posttranslational ER-import became available by a systematic identification of naturally occurring substrates of both pathways. Furthermore, the ectopic expression of proteins in phylogenetically distant species can cause their mislocalization. The profile of proteins imported by N-terminal targeting signals can be modulated by different processes such as secondary modifications of targeting signals and receptors, but also by the expression of several individual receptor proteins, which differ in their substrate specificity and their engagement with different chaperones.
Finally, N-terminal targeting signals can contribute to human diseases as mutations in targeting signals were found to cause inherited human diseases, and intracellular pathogens and viruses equip their proteins with suitable targeting signals to ensure their proper distribution, but also because bacterial signal peptides are specifically recognized as part of the innate immune response. For biotechnological application a better understanding of N-terminal targeting signals will facilitate the improvement of secretory systems for the heterologous production of proteins.
We accept original scientific work and review articles of high quality, which deal with diverse aspects of the properties and functions of N-terminal targeting signals, but also papers which compare them with other types of targeting signals. This may reach from common and specifying properties of these targeting signals to the modes of their interaction with receptor proteins, from regulatory processes modulating their import efficiency to the fate of mislocalized proteins and from patterns of evolutionary change in these signals to their relevance in human diseases such as their utilization by intracellular pathogens or viruses. This issue will be open to different types of methodological approaches covering traditional biochemical, genetic and molecular biological techniques, but also biophysical or bioinformatic approaches with a special appreciation of interdisciplinary work.
Specific protein transport processes are essential to sequester proteins within membrane bound compartments or to export them effectively from cells. Such transport processes are commonly initiated by the interaction of characteristic targeting signals encoded in the primary sequence of proteins and their cognate receptor proteins, which mediate the interaction with the respective general transport machinery across the organellar, ER or bacterial membrane. Targeting signals for mitochondria (presequences), chloroplasts (transit peptides), peroxisomes (type-2 peroxisomal targeting signal, PTS2), but also for the ER (signal peptides) or the bacterial secretion system (signal peptides or signal sequences) share positions at the N-terminal part of the proteins and a characteristic alpha-helical sequence element. A high selectivity of the receptor proteins for different types of targeting signals is a prerequisite for specific protein transport. However, a detailed understanding of the width of diverse physiological functions associated with N-terminal targeting signals is only beginning to develop, which would certainly also benefit from a systematic comparison with other types of targeting signals, including those found internally and at the C-termini of polypeptides.
This Research Topic should broaden the understanding of the nature of N-terminal targeting signals and their diverse physiological roles by bringing together results from systematic analyses, novel biophysical methods and comparative bioinformatics analyses. By this means, the inherent differences between these targeting signals and the specificity of their recognition by receptor proteins should be emphasized. Recent results demonstrated a bilocalization of various mitochondrial and chloroplastic proteins suggesting a lower specificity of transport than anticipated. Moreover, differences in the characteristics of signal peptides mediating co- or posttranslational ER-import became available by a systematic identification of naturally occurring substrates of both pathways. Furthermore, the ectopic expression of proteins in phylogenetically distant species can cause their mislocalization. The profile of proteins imported by N-terminal targeting signals can be modulated by different processes such as secondary modifications of targeting signals and receptors, but also by the expression of several individual receptor proteins, which differ in their substrate specificity and their engagement with different chaperones.
Finally, N-terminal targeting signals can contribute to human diseases as mutations in targeting signals were found to cause inherited human diseases, and intracellular pathogens and viruses equip their proteins with suitable targeting signals to ensure their proper distribution, but also because bacterial signal peptides are specifically recognized as part of the innate immune response. For biotechnological application a better understanding of N-terminal targeting signals will facilitate the improvement of secretory systems for the heterologous production of proteins.
We accept original scientific work and review articles of high quality, which deal with diverse aspects of the properties and functions of N-terminal targeting signals, but also papers which compare them with other types of targeting signals. This may reach from common and specifying properties of these targeting signals to the modes of their interaction with receptor proteins, from regulatory processes modulating their import efficiency to the fate of mislocalized proteins and from patterns of evolutionary change in these signals to their relevance in human diseases such as their utilization by intracellular pathogens or viruses. This issue will be open to different types of methodological approaches covering traditional biochemical, genetic and molecular biological techniques, but also biophysical or bioinformatic approaches with a special appreciation of interdisciplinary work.
