Limits...
N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum.

Forte GM, Pool MR, Stirling CJ - PLoS Biol. (2011)

Bottom Line: Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%-80% of proteins reportedly altered in this way.Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery.Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.

ABSTRACT
Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%-80% of proteins reportedly altered in this way. Here we report a systematic analysis of the predicted N-terminal processing of cytosolic proteins versus those destined to be sorted to the secretory pathway. While cytosolic proteins were profoundly biased in favour of processing, we found an equal and opposite bias against such modification for secretory proteins. Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery. Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species.

Show MeSH
A bias against N-terminal processing of signal sequences is conservedacross eukaroytes.Predicted frequency of an unprocessed initiating methionine in signalsequences from S. cerevisaie(n = 277), C. elegans(n = 378),Drosophila(n = 448), human(n = 595), andArabidopsis(n = 500) compared to the respectiveproteomes as a whole [2]. For complete datasets, see TablesS5 and S6.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3104963&req=5

pbio-1001073-g006: A bias against N-terminal processing of signal sequences is conservedacross eukaroytes.Predicted frequency of an unprocessed initiating methionine in signalsequences from S. cerevisaie(n = 277), C. elegans(n = 378),Drosophila(n = 448), human(n = 595), andArabidopsis(n = 500) compared to the respectiveproteomes as a whole [2]. For complete datasets, see TablesS5 and S6.

Mentions: Having validated the biological significance of the bias observed in ourbioinformatic study, we extended our analysis from yeast to higher eukaryotes (Figure 6). The pattern observed innematodes and insects was remarkably similar to that seen in yeast, with∼70% of signal peptides predicted to retain an unprocessed methioninecompared to only 20% for the proteome as a whole [2]. The trend was similar inhumans and plants, albeit less pronounced, with ∼50% of secretoryN-termini predicted to remain unprocessed compared to 15% for the proteome asa whole [2].Thus this phenomenon appears not to be restricted to fungi but is very widelyconserved.


N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum.

Forte GM, Pool MR, Stirling CJ - PLoS Biol. (2011)

A bias against N-terminal processing of signal sequences is conservedacross eukaroytes.Predicted frequency of an unprocessed initiating methionine in signalsequences from S. cerevisaie(n = 277), C. elegans(n = 378),Drosophila(n = 448), human(n = 595), andArabidopsis(n = 500) compared to the respectiveproteomes as a whole [2]. For complete datasets, see TablesS5 and S6.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104963&req=5

pbio-1001073-g006: A bias against N-terminal processing of signal sequences is conservedacross eukaroytes.Predicted frequency of an unprocessed initiating methionine in signalsequences from S. cerevisaie(n = 277), C. elegans(n = 378),Drosophila(n = 448), human(n = 595), andArabidopsis(n = 500) compared to the respectiveproteomes as a whole [2]. For complete datasets, see TablesS5 and S6.
Mentions: Having validated the biological significance of the bias observed in ourbioinformatic study, we extended our analysis from yeast to higher eukaryotes (Figure 6). The pattern observed innematodes and insects was remarkably similar to that seen in yeast, with∼70% of signal peptides predicted to retain an unprocessed methioninecompared to only 20% for the proteome as a whole [2]. The trend was similar inhumans and plants, albeit less pronounced, with ∼50% of secretoryN-termini predicted to remain unprocessed compared to 15% for the proteome asa whole [2].Thus this phenomenon appears not to be restricted to fungi but is very widelyconserved.

Bottom Line: Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%-80% of proteins reportedly altered in this way.Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery.Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.

ABSTRACT
Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%-80% of proteins reportedly altered in this way. Here we report a systematic analysis of the predicted N-terminal processing of cytosolic proteins versus those destined to be sorted to the secretory pathway. While cytosolic proteins were profoundly biased in favour of processing, we found an equal and opposite bias against such modification for secretory proteins. Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery. Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species.

Show MeSH