title: The similarity between N-terminal targeting signals for protein import into different organelles and its evolutionary relevance.
abstract: The proper distribution of proteins between the cytosol and various membrane-bound compartments is crucial for the functionality of eukaryotic cells. This requires the cooperation between protein transport machineries that translocate diverse proteins from the cytosol into these compartments and targeting signal(s) encoded within the primary sequence of these proteins that define their cellular destination. The mechanisms exerting protein translocation differ remarkably between the compartments, but the predominant targeting signals for mitochondria, chloroplasts and the ER share the N-terminal position, an α-helical structural element and the removal from the core protein by intraorganellar cleavage. Interestingly, similar properties have been described for the peroxisomal targeting signal type 2 mediating the import of a fraction of soluble peroxisomal proteins, whereas other peroxisomal matrix proteins encode the type 1 targeting signal residing at the extreme C-terminus. The structural similarity of N-terminal targeting signals poses a challenge to the specificity of protein transport, but allows the generation of ambiguous targeting signals that mediate dual targeting of proteins into different compartments. Dual targeting might represent an advantage for adaptation processes that involve a redistribution of proteins, because it circumvents the hierarchy of targeting signals. Thus, the co-existence of two equally functional import pathways into peroxisomes might reflect a balance between evolutionary constant and flexible transport routes.
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Kunze
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
keywords: PTS2; Peroxisomes; ambiguous targeting signals; preprotein; signal peptide; specificity; targeting signals; transit peptide