A new study reveals a functional rule for N-terminal acetylation in higher eukaryotes called the (X)PX rule and describes a generic method that prevents this modification to allow the study of N-terminal acetylation in any given protein

Aebersold, Ruedi

Ahrens, Christian H.

Basler, Konrad

Brunner, Erich

Gerrits, Bertran

Gevaert, Kris

Goetze, Sandra

Hafen, Ernst

Laczko, Endre

Lange, Vinzenz

Mohanty, Sonali

Mosimann, Christian

Niederer, Eva M.

Qeli, Ermir

Roschitzki, Bernd

Staes, An

Timmerman, Evy

Vandekerckhove, Joël

PLoS Biology

English

PubMed

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X)PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X)PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species

Sandra Goetze

Ermir Qeli

Christian Mosimann

An Staes

Bertran Gerrits

Bernd Roschitzki

Sonali Mohanty

Eva M Niederer

Endre Laczko

Evy Timmerman

Vinzenz Lange

Ernst Hafen

Ruedi Aebersold

Joël Vandekerckhove

Konrad Basler

Christian H Ahrens

Kris Gevaert

Erich Brunner

Directory of Open Access Journals

Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

Goetze Sandra

Qeli Ermir

Mosimann Christian

Staes An

Gerrits Bertran

Roschitzki Bernd

Mohanty Sonali

Niederer Eva M.

Laczko Endre

Timmerman Evy

Lange Vinzenz

Hafen Ernst

Aebersold Ruedi

Vandekerckhove Joël

Basler Konrad

Ahrens Christian H.

Gevaert Kris

Brunner Erich

Public Library of Science (PLOS)

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X)PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X)PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species.ISSN:1544-9173ISSN:1545-788

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Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X) PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X) PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species

Goetze, S

Qeli, E

Mosimann, C

Gerrits, B

Roschitzki, B

Mohanty, S

Niederer, EM

Laczko, E

Lange, V

Hafen, E

Aebersold, R

Basler, K

Ahrens, CH

Brunner, E

Ghent University Academic Bibliography

Staes, A

Niederer, E M

Timmerman, E

Vandekerckhove, J

Ahrens, C H

Gevaert, K

ZORA

Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster

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http://www.zora.uzh.ch/28633/1/Goetze_Plos_Biol_2009_V.pdf

Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster

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