Archaeal N-terminal Protein Maturation Commonly Involves N-terminal Acetylation: A Large-scale Proteomics Survey

Falb, Michaela; Aivaliotis, Michalis; Garcia-Rizo, Carolina; Bisle, Birgit; Tebbe, Andreas; Klein, Christian; Konstantinidis, Kosta; Siedler, Frank; Pfeiffer, Friedhelm; Oesterhelt, Dieter

doi:10.1016/j.jmb.2006.07.086

Cited by 80 publications

(98 citation statements)

References 33 publications

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“…Moreover, it is very common to observe the cleavage of initial methionine in H. salinarum [40]. Therefore we searched for confidently identified peptides matching the first semi-tryptic peptide of predicted isoforms, including or not the first amino acid.…”

Section: Resultsmentioning

confidence: 99%

Internal RNAs overlapping coding sequences can drive the production of alternative proteins in archaea

et al. 2018

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Prokaryotic genomes show a high level of information compaction often with different molecules transcribed from the same locus. Although antisense RNAs have been relatively well studied, RNAs in the same strand, internal RNAs (intraRNAs), are still poorly understood. The question of how common is the translation of overlapping reading frames remains open. We address this question in the model archaeon Halobacterium salinarum. In the present work we used differential RNA-seq (dRNA-seq) in H. salinarum NRC-1 to locate intraRNA signals in subsets of internal transcription start sites (iTSS) and establish the open reading frames associated to them (intraORFs). Using C-terminally flagged proteins, we experimentally observed isoforms accurately predicted by intraRNA translation for kef1, acs3 and orc4 genes. We also recovered from the literature and mass spectrometry databases several instances of protein isoforms consistent with intraRNA translation such as the gas vesicle protein gene gvpC1. We found evidence for intraRNAs in horizontally transferred genes such as the chaperone dnaK and the aerobic respiration related cydA in both H. salinarum and Escherichia coli. Also, intraRNA translation evidence in H. salinarum, E. coli and yeast of a universal elongation factor (aEF-2, fusA and eEF-2) suggests that this is an ancient phenomenon present in all domains of life.

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Section: Resultsmentioning

confidence: 99%

Internal RNAs overlapping coding sequences can drive the production of alternative proteins in archaea

et al. 2018

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“…8A). These global studies have been extended to archaea (N-terminal acetylation) (140), bacteria (141)(142)(143), plants (144), parasites (145,146), and humans (147), helping cement the fundamental principles and contributions of acetylation to cellular physiology. Such global studies consistently suggest that acetylation controls diverse cellular processes, including metabolism, transcription, translation, and cell structure.…”

Section: High-throughput Identification Of Acetylated Proteins Globalmentioning

confidence: 99%

Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress

Hentchel

Escalante‐Semerena

2015

Microbiol Mol Biol Rev

163

175

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SUMMARY Acylation of biomolecules (e.g., proteins and small molecules) is a process that occurs in cells of all domains of life and has emerged as a critical mechanism for the control of many aspects of cellular physiology, including chromatin maintenance, transcriptional regulation, primary metabolism, cell structure, and likely other cellular processes. Although this review focuses on the use of acetyl moieties to modify a protein or small molecule, it is clear that cells can use many weak organic acids (e.g., short-, medium-, and long-chain mono- and dicarboxylic aliphatics and aromatics) to modify a large suite of targets. Acetylation of biomolecules has been studied for decades within the context of histone-dependent regulation of gene expression and antibiotic resistance. It was not until the early 2000s that the connection between metabolism, physiology, and protein acetylation was reported. This was the first instance of a metabolic enzyme (acetyl coenzyme A [acetyl-CoA] synthetase) whose activity was controlled by acetylation via a regulatory system responsive to physiological cues. The above-mentioned system was comprised of an acyltransferase and a partner deacylase. Given the reversibility of the acylation process, this system is also referred to as r eversible l ysine a cylation (RLA). A wealth of information has been obtained since the discovery of RLA in prokaryotes, and we are just beginning to visualize the extent of the impact that this regulatory system has on cell function.

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“…These structures and their accompanying biochemical characterization have provided significant insight into the mechanisms of substrate specificity and catalysis used by NAT enzymes. Interestingly, although NatA and NatE both catalyze α-amino group acetylation, they use unique catalytic strategies and substantially different substrate amino-terminal residue binding pockets to achieve sequence-based substrate specificity.Although only six amino-terminally acetylated proteins have been identified in Escherichia coli, large-scale proteomics studies of three different archaeal species revealed that ∼14-29% of all proteins isolated are acetylated at their amino terminus (17)(18)(19)(20). Analysis of the thermophilic archaea Sulfolobus solfataricus genome resulted in the identification of a protein with 37% sequence identity to human NAA10 that is believed to be the only NAT in this species (21).…”

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confidence: 99%

“…Although only six amino-terminally acetylated proteins have been identified in Escherichia coli, large-scale proteomics studies of three different archaeal species revealed that ∼14-29% of all proteins isolated are acetylated at their amino terminus (17)(18)(19)(20). Analysis of the thermophilic archaea Sulfolobus solfataricus genome resulted in the identification of a protein with 37% sequence identity to human NAA10 that is believed to be the only NAT in this species (21).…”

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confidence: 99%

Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog

Liszczak

Marmorstein

2013

Proc. Natl. Acad. Sci. U.S.A.

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Amino-terminal acetylation is a ubiquitous modification in eukaryotes that is involved in a growing number of biological processes. There are six known eukaryotic amino-terminal acetyltransferases (NATs), which are differentiated from one another on the basis of substrate specificity. To date, two eukaryotic NATs, NatA and NatE, have been structurally characterized, of which NatA will acetylate the α-amino group of a number of nonmethionine amino-terminal residue substrates such as serine; NatE requires a substrate amino-terminal methionine residue for activity. Interestingly, these two NATs use different catalytic strategies to accomplish substrate-specific acetylation. In archaea, where this modification is less prevalent, only one NAT enzyme has been identified. Surprisingly, this enzyme is able to acetylate NatA and NatE substrates and is believed to represent an ancestral NAT variant from which the eukaryotic NAT machinery evolved. To gain insight into the evolution of NAT enzymes, we determined the X-ray crystal structure of an archaeal NAT from Sulfolobus solfataricus (ssNAT). Through the use of mutagenesis and kinetic analysis, we show that the active site of ssNAT represents a hybrid of the NatA and NatE active sites, and we highlight features of this protein that allow it to facilitate catalysis of distinct substrates through different catalytic strategies, which is a unique characteristic of this enzyme. Taken together, the structural and biochemical data presented here have implications for the evolution of eukaryotic NAT enzymes and the substrate specificities therein.structural biology | evolutionary biology | enzymology | X-ray crystallography T he cotranslational process of amino-terminal acetylation occurs on a majority of eukaryotic proteins and mediates many biological processes, including cellular apoptosis, enzymatic regulation, protein localization, and protein degradation (1-4). In humans, three major amino-terminal acetyltransferase (NAT) complexes, called NatA, NatB, and NatC, are responsible for modifying ∼85% of all proteins that undergo amino-terminal acetylation (5). These complexes are conserved in yeast, exist as obligate heterodimers, and are differentiated from one another on the basis of substrate specificity, which is dictated by the amino-terminal sequence of the substrate protein (5, 6). Each complex consists of a single unique catalytic subunit and an additional unique auxiliary subunit that has been shown to potentiate activity and alter substrate specificity of the enzymatic component, as well as anchor the complex to the ribosome during translation (6-11). Three additional human NAT enzymes, NatD-NatF, have also been identified, but they have a much more limited set of physiological substrates, appear to be independently active, and are not well characterized across eukaryotes (12)(13)(14).The only two eukaryotic NATs that have been structurally characterized are Schizosaccharomyces pombe NatA, consisting of the Naa10p catalytic subunit and Naa15p regulatory subunit, and ...

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Archaeal N-terminal Protein Maturation Commonly Involves N-terminal Acetylation: A Large-scale Proteomics Survey

Cited by 80 publications

References 33 publications

Internal RNAs overlapping coding sequences can drive the production of alternative proteins in archaea

Internal RNAs overlapping coding sequences can drive the production of alternative proteins in archaea

Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress

Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog

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