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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.


N-terminal targeting signals determine the transport route of proteins by the interaction with the receptor proteins. (A)Competition of receptor proteins: the N-terminal amino acid sequence of a newly synthesized protein can interact with all receptor proteins, which compete for the peptide sequence (peroxisomal Pex7, mitochondrial Tom20, chloroplast Toc34, and Srp54 for the ER) and with additional cytosolic proteins that might affect these interactions (Hsp70, Hsp90, 14-3-3 proteins). The choice of the transport route is based on the relative affinity of the peptide sequence to different receptor proteins. (B)Different import mechanisms generate a hierarchy of targeting signals: An N-terminal amino acid sequence is sequentially scanned by diverse receptor proteins, because these interactions occur at different time points during the production and folding of the protein. A newly synthesized protein either binds to the SRP to become translated into ER or it finishes translation in the cytosol [1] Next, the protein either becomes folded or remains unfolded due to its interaction with chaperones, [2] Unfolded proteins can interact with the mitochondrial receptor Tom20, the chloroplast receptor Toc34 or the Sec61 complex of the ER (translocon), [3] Finally, folded proteins can either interact with the soluble receptor protein Pex7, which initiates their transport into peroxisomes, or they remain in the cytosol [4].
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Figure 3: N-terminal targeting signals determine the transport route of proteins by the interaction with the receptor proteins. (A)Competition of receptor proteins: the N-terminal amino acid sequence of a newly synthesized protein can interact with all receptor proteins, which compete for the peptide sequence (peroxisomal Pex7, mitochondrial Tom20, chloroplast Toc34, and Srp54 for the ER) and with additional cytosolic proteins that might affect these interactions (Hsp70, Hsp90, 14-3-3 proteins). The choice of the transport route is based on the relative affinity of the peptide sequence to different receptor proteins. (B)Different import mechanisms generate a hierarchy of targeting signals: An N-terminal amino acid sequence is sequentially scanned by diverse receptor proteins, because these interactions occur at different time points during the production and folding of the protein. A newly synthesized protein either binds to the SRP to become translated into ER or it finishes translation in the cytosol [1] Next, the protein either becomes folded or remains unfolded due to its interaction with chaperones, [2] Unfolded proteins can interact with the mitochondrial receptor Tom20, the chloroplast receptor Toc34 or the Sec61 complex of the ER (translocon), [3] Finally, folded proteins can either interact with the soluble receptor protein Pex7, which initiates their transport into peroxisomes, or they remain in the cytosol [4].

Mentions: Although the N-terminal targeting signals for mitochondria, chloroplasts, the ER and also for peroxisomes (PTS2) are structurally similar, the accurate distribution of proteins between different subcellular compartments demonstrates that protein transport is highly specific. At first glance, the N-terminal amino acid sequence of a newly synthesized protein is concomitantly exposed to all available receptor proteins, which compete for the N-terminal sequence (Figure 3A). Accordingly, the specificity of protein transport can only be achieved by promoting the interaction between an N-terminal amino acid sequence and its appropriate receptor protein, whereas interactions with undesired receptor proteins that would induce mistargeting must be avoided. However, in reality the different receptor proteins scan an N-terminal amino acid sequence during distinct phases of protein formation, because of the different mechanisms of protein import (Figure 3B). The recognition of a signal can occur either directly upon its appearance at the exit site of the ribosome (signal peptide), or after translation, when the unfolded protein reaches the organellar membrane (presequence, transit peptide, signal peptide) or after completion of protein folding (peroxisomal targeting signal). This implicates that an early decision in favor of one transport route might exclude other routes that are initiated by receptor interactions at a later stage of protein formation. Thus, the properties of the protein import machineries modulate the specificity of protein transport, although the relative affinity of an N-terminal amino acid sequence to different receptor proteins remains a crucial determinant for the choice of the transport route.


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

Kunze M, Berger J - Front Physiol (2015)

N-terminal targeting signals determine the transport route of proteins by the interaction with the receptor proteins. (A)Competition of receptor proteins: the N-terminal amino acid sequence of a newly synthesized protein can interact with all receptor proteins, which compete for the peptide sequence (peroxisomal Pex7, mitochondrial Tom20, chloroplast Toc34, and Srp54 for the ER) and with additional cytosolic proteins that might affect these interactions (Hsp70, Hsp90, 14-3-3 proteins). The choice of the transport route is based on the relative affinity of the peptide sequence to different receptor proteins. (B)Different import mechanisms generate a hierarchy of targeting signals: An N-terminal amino acid sequence is sequentially scanned by diverse receptor proteins, because these interactions occur at different time points during the production and folding of the protein. A newly synthesized protein either binds to the SRP to become translated into ER or it finishes translation in the cytosol [1] Next, the protein either becomes folded or remains unfolded due to its interaction with chaperones, [2] Unfolded proteins can interact with the mitochondrial receptor Tom20, the chloroplast receptor Toc34 or the Sec61 complex of the ER (translocon), [3] Finally, folded proteins can either interact with the soluble receptor protein Pex7, which initiates their transport into peroxisomes, or they remain in the cytosol [4].
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Figure 3: N-terminal targeting signals determine the transport route of proteins by the interaction with the receptor proteins. (A)Competition of receptor proteins: the N-terminal amino acid sequence of a newly synthesized protein can interact with all receptor proteins, which compete for the peptide sequence (peroxisomal Pex7, mitochondrial Tom20, chloroplast Toc34, and Srp54 for the ER) and with additional cytosolic proteins that might affect these interactions (Hsp70, Hsp90, 14-3-3 proteins). The choice of the transport route is based on the relative affinity of the peptide sequence to different receptor proteins. (B)Different import mechanisms generate a hierarchy of targeting signals: An N-terminal amino acid sequence is sequentially scanned by diverse receptor proteins, because these interactions occur at different time points during the production and folding of the protein. A newly synthesized protein either binds to the SRP to become translated into ER or it finishes translation in the cytosol [1] Next, the protein either becomes folded or remains unfolded due to its interaction with chaperones, [2] Unfolded proteins can interact with the mitochondrial receptor Tom20, the chloroplast receptor Toc34 or the Sec61 complex of the ER (translocon), [3] Finally, folded proteins can either interact with the soluble receptor protein Pex7, which initiates their transport into peroxisomes, or they remain in the cytosol [4].
Mentions: Although the N-terminal targeting signals for mitochondria, chloroplasts, the ER and also for peroxisomes (PTS2) are structurally similar, the accurate distribution of proteins between different subcellular compartments demonstrates that protein transport is highly specific. At first glance, the N-terminal amino acid sequence of a newly synthesized protein is concomitantly exposed to all available receptor proteins, which compete for the N-terminal sequence (Figure 3A). Accordingly, the specificity of protein transport can only be achieved by promoting the interaction between an N-terminal amino acid sequence and its appropriate receptor protein, whereas interactions with undesired receptor proteins that would induce mistargeting must be avoided. However, in reality the different receptor proteins scan an N-terminal amino acid sequence during distinct phases of protein formation, because of the different mechanisms of protein import (Figure 3B). The recognition of a signal can occur either directly upon its appearance at the exit site of the ribosome (signal peptide), or after translation, when the unfolded protein reaches the organellar membrane (presequence, transit peptide, signal peptide) or after completion of protein folding (peroxisomal targeting signal). This implicates that an early decision in favor of one transport route might exclude other routes that are initiated by receptor interactions at a later stage of protein formation. Thus, the properties of the protein import machineries modulate the specificity of protein transport, although the relative affinity of an N-terminal amino acid sequence to different receptor proteins remains a crucial determinant for the choice of the transport route.

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.