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Towards a functional understanding of protein N-terminal acetylation.

Arnesen T - PLoS Biol. (2011)

Bottom Line: Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic.However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins.These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway. thomas.arnesen@mbi.uib.no

ABSTRACT
Protein N-terminal acetylation is a major modification of eukaryotic proteins. Its functional implications include regulation of protein-protein interactions and targeting to membranes, as demonstrated by studies of a handful of proteins. Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic. However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins. These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

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Schematic overview of N-terminal processing in eukaryotes.N-termini with small amino acid residues in the second position (Met-Xxx-)are mostly processed by methionine aminopeptidase (MAP), whereafter thenewly generated N-termini may be acetylated by NatA (*or by NatD in thecase of histones H2A and H4). This class of N-termini may also be acetylatedon the initiator methionine (iMet) by unknown NATs or by NatF, which isspecific for higher eukaryotes. N-termini with larger amino acid residues inthe second position (Met-Yyy-) are not normally cleaved by MAPs, butpotentially acetylated directly on the iMet by a variety of NATs dependingon the N-terminal sequence. NatB potentially acetylates N-termini withacidic or hydrophilic residues in the second position. Hydrophobic N-terminiare acetylated by NatC and potentially NatE, and in higher eukaryotes alsoNatF. NatF and perhaps other NATs acetylate Met-Met- and Met-Lys- N-termini.Information derived from [8] and references herein and NatF identification (P.Van Damme, K. Hole, A. Pimenta-Marques, J. Vandekerckhove, R. G. Martinho,et al., unpublished data).
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pbio-1001074-g001: Schematic overview of N-terminal processing in eukaryotes.N-termini with small amino acid residues in the second position (Met-Xxx-)are mostly processed by methionine aminopeptidase (MAP), whereafter thenewly generated N-termini may be acetylated by NatA (*or by NatD in thecase of histones H2A and H4). This class of N-termini may also be acetylatedon the initiator methionine (iMet) by unknown NATs or by NatF, which isspecific for higher eukaryotes. N-termini with larger amino acid residues inthe second position (Met-Yyy-) are not normally cleaved by MAPs, butpotentially acetylated directly on the iMet by a variety of NATs dependingon the N-terminal sequence. NatB potentially acetylates N-termini withacidic or hydrophilic residues in the second position. Hydrophobic N-terminiare acetylated by NatC and potentially NatE, and in higher eukaryotes alsoNatF. NatF and perhaps other NATs acetylate Met-Met- and Met-Lys- N-termini.Information derived from [8] and references herein and NatF identification (P.Van Damme, K. Hole, A. Pimenta-Marques, J. Vandekerckhove, R. G. Martinho,et al., unpublished data).

Mentions: Unlike most other protein modifications, Nt-acetylation is irreversible; it occursmainly during the synthesis of the protein, catalyzed by N-terminalacetyltransferases (NATs) associated with ribosomes [4]–[7] (Figure 1 and Figure 2, point 1). There are severaldistinct NATs in eukaryotes—NatA‐NatF—each composed of one ormore subunits and each acetylating a specific subgroup of N‐termini dependingon the amino acid sequence of the first few amino acids [8]. The Nt‐acetylationpatterns and the NAT machinery appear to be similar in all organisms from lowereukaryotes like the yeast Saccharomyces cerevisiae to highereukaryotes [1],[9], [10], althoughhigher eukaryotes have more protein Nt‐acetylation and express more NATs thanyeast do [1],[8].


Towards a functional understanding of protein N-terminal acetylation.

Arnesen T - PLoS Biol. (2011)

Schematic overview of N-terminal processing in eukaryotes.N-termini with small amino acid residues in the second position (Met-Xxx-)are mostly processed by methionine aminopeptidase (MAP), whereafter thenewly generated N-termini may be acetylated by NatA (*or by NatD in thecase of histones H2A and H4). This class of N-termini may also be acetylatedon the initiator methionine (iMet) by unknown NATs or by NatF, which isspecific for higher eukaryotes. N-termini with larger amino acid residues inthe second position (Met-Yyy-) are not normally cleaved by MAPs, butpotentially acetylated directly on the iMet by a variety of NATs dependingon the N-terminal sequence. NatB potentially acetylates N-termini withacidic or hydrophilic residues in the second position. Hydrophobic N-terminiare acetylated by NatC and potentially NatE, and in higher eukaryotes alsoNatF. NatF and perhaps other NATs acetylate Met-Met- and Met-Lys- N-termini.Information derived from [8] and references herein and NatF identification (P.Van Damme, K. Hole, A. Pimenta-Marques, J. Vandekerckhove, R. G. Martinho,et al., unpublished data).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104970&req=5

pbio-1001074-g001: Schematic overview of N-terminal processing in eukaryotes.N-termini with small amino acid residues in the second position (Met-Xxx-)are mostly processed by methionine aminopeptidase (MAP), whereafter thenewly generated N-termini may be acetylated by NatA (*or by NatD in thecase of histones H2A and H4). This class of N-termini may also be acetylatedon the initiator methionine (iMet) by unknown NATs or by NatF, which isspecific for higher eukaryotes. N-termini with larger amino acid residues inthe second position (Met-Yyy-) are not normally cleaved by MAPs, butpotentially acetylated directly on the iMet by a variety of NATs dependingon the N-terminal sequence. NatB potentially acetylates N-termini withacidic or hydrophilic residues in the second position. Hydrophobic N-terminiare acetylated by NatC and potentially NatE, and in higher eukaryotes alsoNatF. NatF and perhaps other NATs acetylate Met-Met- and Met-Lys- N-termini.Information derived from [8] and references herein and NatF identification (P.Van Damme, K. Hole, A. Pimenta-Marques, J. Vandekerckhove, R. G. Martinho,et al., unpublished data).
Mentions: Unlike most other protein modifications, Nt-acetylation is irreversible; it occursmainly during the synthesis of the protein, catalyzed by N-terminalacetyltransferases (NATs) associated with ribosomes [4]–[7] (Figure 1 and Figure 2, point 1). There are severaldistinct NATs in eukaryotes—NatA‐NatF—each composed of one ormore subunits and each acetylating a specific subgroup of N‐termini dependingon the amino acid sequence of the first few amino acids [8]. The Nt‐acetylationpatterns and the NAT machinery appear to be similar in all organisms from lowereukaryotes like the yeast Saccharomyces cerevisiae to highereukaryotes [1],[9], [10], althoughhigher eukaryotes have more protein Nt‐acetylation and express more NATs thanyeast do [1],[8].

Bottom Line: Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic.However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins.These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway. thomas.arnesen@mbi.uib.no

ABSTRACT
Protein N-terminal acetylation is a major modification of eukaryotic proteins. Its functional implications include regulation of protein-protein interactions and targeting to membranes, as demonstrated by studies of a handful of proteins. Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic. However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins. These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

Show MeSH
Related in: MedlinePlus