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The similarity between N-terminal targeting signals for protein import into different organelles and its evolutionary relevance.

Kunze M, Berger J - Front Physiol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna Vienna, Austria.

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.

No MeSH data available.


Mechanisms to provide the same enzymatic activity or protein function within different subcellular compartments. Bilocalization of protein(s) requires the presence of two alternative targeting signals, which can be either encoded by alternative N-terminal sequences (upper part) or can be encoded by an N-terminal targeting signal and a C-terminal PTS1, respectively (lower part). (A) Two independent genes code for proteins with the same enzymatic activity of function (isoenzymes/homologoues), which harbor different targeting signals. (B) Two variants of the same protein are generated from a single gene, which share the core domain(s), but differ in the encoded targeting signals; variants encoding alternative N-terminal sequences can be obtained by [i] alternative splicing from the same pre-mRNA with a non-coding first exon or [ii] by alternative transcription initiation generating alternative first exons, which use to the same splice acceptor site of the second exon. Variants with and without N-terminal targeting signal, but sharing a C-terminal PTS1 can be generated by [iii] exon skipping behind the first non-coding exon, which omits the second exon encoding the N-terminal targeting signal, [iv] alternative transcription initiation ablating the first exon and [v] alternative translation initiation at different start codons within the same mRNA. (C) One protein is equipped with an ambiguous targeting signal, which is sufficient to mediate the concomitant targeting of the protein to more than one organelle.
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Figure 4: Mechanisms to provide the same enzymatic activity or protein function within different subcellular compartments. Bilocalization of protein(s) requires the presence of two alternative targeting signals, which can be either encoded by alternative N-terminal sequences (upper part) or can be encoded by an N-terminal targeting signal and a C-terminal PTS1, respectively (lower part). (A) Two independent genes code for proteins with the same enzymatic activity of function (isoenzymes/homologoues), which harbor different targeting signals. (B) Two variants of the same protein are generated from a single gene, which share the core domain(s), but differ in the encoded targeting signals; variants encoding alternative N-terminal sequences can be obtained by [i] alternative splicing from the same pre-mRNA with a non-coding first exon or [ii] by alternative transcription initiation generating alternative first exons, which use to the same splice acceptor site of the second exon. Variants with and without N-terminal targeting signal, but sharing a C-terminal PTS1 can be generated by [iii] exon skipping behind the first non-coding exon, which omits the second exon encoding the N-terminal targeting signal, [iv] alternative transcription initiation ablating the first exon and [v] alternative translation initiation at different start codons within the same mRNA. (C) One protein is equipped with an ambiguous targeting signal, which is sufficient to mediate the concomitant targeting of the protein to more than one organelle.

Mentions: The concurrent presence of a protein function or protein activity within different subcellular compartments can be achieved by various means (Figure 4). In the traditional concept, the bilocalization of a protein function is realized by independently encoded homologous proteins that are equipped with different targeting signals (Figure 4A). These signals can either be both located at the N-termini of the proteins (upper part) or at opposite ends (lower part). Alternatively, the cell can produce different protein variants (isoforms) derived from one gene that share the core domain, but differ slightly in their primary sequence, which is sufficient to exchange targeting signals (Figure 4B). In this process, either variants with alternative N-terminal amino acid sequences are generated that differ by the encoded targeting signal (upper part) or variants are produced that share a C-terminal PTS1, but encode or lack an additional N-terminal targeting signal (lower part). Protein variants with alternative N-terminal sequences (upper panel) can be generated from a single gene by the production of different mRNAs that are obtained either by alternative splicing of the same pre-mRNA or by alternative transcription initiation based on different promoters that generate different pre-mRNAs (Mueller et al., 2004; Yogev and Pines, 2011). Protein variants that encode targeting signals at the opposite ends of the protein probably necessitate the omission of the N-terminal targeting signal to disclose a functional PTS1 (lower panel). Thus, the two protein variants should differ in the absence or presence of the N-terminal targeting signal, which can be achieved by the omission of the N-terminal part of the protein sequence either by alternative translation initiation or leaky ribosome scanning (Elgersma et al., 1995; Wamboldt et al., 2009), next to the abovementioned mechanisms of alternative splicing and alternative transcription initiation (Ast et al., 2013).


The similarity between N-terminal targeting signals for protein import into different organelles and its evolutionary relevance.

Kunze M, Berger J - Front Physiol (2015)

Mechanisms to provide the same enzymatic activity or protein function within different subcellular compartments. Bilocalization of protein(s) requires the presence of two alternative targeting signals, which can be either encoded by alternative N-terminal sequences (upper part) or can be encoded by an N-terminal targeting signal and a C-terminal PTS1, respectively (lower part). (A) Two independent genes code for proteins with the same enzymatic activity of function (isoenzymes/homologoues), which harbor different targeting signals. (B) Two variants of the same protein are generated from a single gene, which share the core domain(s), but differ in the encoded targeting signals; variants encoding alternative N-terminal sequences can be obtained by [i] alternative splicing from the same pre-mRNA with a non-coding first exon or [ii] by alternative transcription initiation generating alternative first exons, which use to the same splice acceptor site of the second exon. Variants with and without N-terminal targeting signal, but sharing a C-terminal PTS1 can be generated by [iii] exon skipping behind the first non-coding exon, which omits the second exon encoding the N-terminal targeting signal, [iv] alternative transcription initiation ablating the first exon and [v] alternative translation initiation at different start codons within the same mRNA. (C) One protein is equipped with an ambiguous targeting signal, which is sufficient to mediate the concomitant targeting of the protein to more than one organelle.
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Related In: Results  -  Collection

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Show All Figures
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Figure 4: Mechanisms to provide the same enzymatic activity or protein function within different subcellular compartments. Bilocalization of protein(s) requires the presence of two alternative targeting signals, which can be either encoded by alternative N-terminal sequences (upper part) or can be encoded by an N-terminal targeting signal and a C-terminal PTS1, respectively (lower part). (A) Two independent genes code for proteins with the same enzymatic activity of function (isoenzymes/homologoues), which harbor different targeting signals. (B) Two variants of the same protein are generated from a single gene, which share the core domain(s), but differ in the encoded targeting signals; variants encoding alternative N-terminal sequences can be obtained by [i] alternative splicing from the same pre-mRNA with a non-coding first exon or [ii] by alternative transcription initiation generating alternative first exons, which use to the same splice acceptor site of the second exon. Variants with and without N-terminal targeting signal, but sharing a C-terminal PTS1 can be generated by [iii] exon skipping behind the first non-coding exon, which omits the second exon encoding the N-terminal targeting signal, [iv] alternative transcription initiation ablating the first exon and [v] alternative translation initiation at different start codons within the same mRNA. (C) One protein is equipped with an ambiguous targeting signal, which is sufficient to mediate the concomitant targeting of the protein to more than one organelle.
Mentions: The concurrent presence of a protein function or protein activity within different subcellular compartments can be achieved by various means (Figure 4). In the traditional concept, the bilocalization of a protein function is realized by independently encoded homologous proteins that are equipped with different targeting signals (Figure 4A). These signals can either be both located at the N-termini of the proteins (upper part) or at opposite ends (lower part). Alternatively, the cell can produce different protein variants (isoforms) derived from one gene that share the core domain, but differ slightly in their primary sequence, which is sufficient to exchange targeting signals (Figure 4B). In this process, either variants with alternative N-terminal amino acid sequences are generated that differ by the encoded targeting signal (upper part) or variants are produced that share a C-terminal PTS1, but encode or lack an additional N-terminal targeting signal (lower part). Protein variants with alternative N-terminal sequences (upper panel) can be generated from a single gene by the production of different mRNAs that are obtained either by alternative splicing of the same pre-mRNA or by alternative transcription initiation based on different promoters that generate different pre-mRNAs (Mueller et al., 2004; Yogev and Pines, 2011). Protein variants that encode targeting signals at the opposite ends of the protein probably necessitate the omission of the N-terminal targeting signal to disclose a functional PTS1 (lower panel). Thus, the two protein variants should differ in the absence or presence of the N-terminal targeting signal, which can be achieved by the omission of the N-terminal part of the protein sequence either by alternative translation initiation or leaky ribosome scanning (Elgersma et al., 1995; Wamboldt et al., 2009), next to the abovementioned mechanisms of alternative splicing and alternative transcription initiation (Ast et al., 2013).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna Vienna, Austria.

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.

No MeSH data available.