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A prokaryotic twist on argonaute function.

Willkomm S, Zander A, Gust A, Grohmann D - Life (Basel) (2015)

Bottom Line: Argonaute proteins can be found in all three domains of life.Despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic Argonaute proteins, the biological function of bacterial and archaeal Argonautes has remained elusive.We especially focus on archaeal Argonautes when discussing the details of the structural and dynamic features in Argonaute that promote substrate recognition and cleavage, thereby revealing differences and similarities in Argonaute biology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, Universitätsklinikum Schleswig-Holstein, University of Lübeck, 23538 Lübeck, Germany. willkomm@imm.uni-luebeck.de.

ABSTRACT
Argonaute proteins can be found in all three domains of life. In eukaryotic organisms, Argonaute is, as the functional core of the RNA-silencing machinery, critically involved in the regulation of gene expression. Despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic Argonaute proteins, the biological function of bacterial and archaeal Argonautes has remained elusive. This review discusses new findings in the field that shed light on the structure and function of Argonaute. We especially focus on archaeal Argonautes when discussing the details of the structural and dynamic features in Argonaute that promote substrate recognition and cleavage, thereby revealing differences and similarities in Argonaute biology.

No MeSH data available.


Overall architecture of Argonaute from the three domains of life. The domain composition (left) and structures (middle) of the bacterial (based on Thermus thermophilus, PDB: 3DLH), the archaeal (based on Pyrococcus furiosus, PDB: 1U04) and the eukaryotic (based on human Argonaute 2, PDB: 4EI3) Argonaute reveal an evolutionarily conserved architecture. Differences can be found in the surface charge distribution of Argonaute proteins (negatively-charged surfaces in red; positively-charged surfaces in blue). The binding pocket for the 5'-end of the guide in the MID domain is highlighted with a green circle.
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life-05-00538-f001: Overall architecture of Argonaute from the three domains of life. The domain composition (left) and structures (middle) of the bacterial (based on Thermus thermophilus, PDB: 3DLH), the archaeal (based on Pyrococcus furiosus, PDB: 1U04) and the eukaryotic (based on human Argonaute 2, PDB: 4EI3) Argonaute reveal an evolutionarily conserved architecture. Differences can be found in the surface charge distribution of Argonaute proteins (negatively-charged surfaces in red; positively-charged surfaces in blue). The binding pocket for the 5'-end of the guide in the MID domain is highlighted with a green circle.

Mentions: The Argonaute (Ago) protein family was initially discovered in eukaryotes [1,2], but orthologs were found in many archaeal and bacterial organisms [3,4,5]. In eukaryotic organisms, Argonaute represents the principal component of the RNA silencing machinery. Despite the advancements in the understanding of Argonaute function in the eukaryotic field, the biological role of prokaryotic Argonaute proteins (pAgo) remained unknown for a long time. Argonaute proteins are encoded in ~32% and 9% of the sequenced archaeal and bacterial genomes, respectively [6]. PAgos were found to cluster in two groups distinguished by the presence or absence of the PAZ domain [5]. A lack of the PAZ domain often coincides with an apparent inactivation of the nuclease activity [5,6]. Interestingly, pAgos are often found in operons with a diverse range of endonucleolytic DNases (nucleases of the restriction endonuclease fold, a distinctive Sirtuin family domain or TIR domain proteins) and/or helicases (e.g., of the DinG-class) [3,5,7], leading to the hypothesis that the co-action of pAgo and an endo-DNase might act as a plasmid/phage restriction system. However, the subset of pAgos that exhibit a high sequence similarity to their eukaryotic counterpart does not seem to show conserved operonic associations with any other genes. Ago is composed of the N-terminal, PAZ (Piwi-Argonaute-Zwille), middle (MID) and PIWI (P-element-induced wimpy testis) domains interconnected by two structured linker regions (Figure 1 and Figure 2). This review mainly discusses the “long” pAgo variants, which share a comparable domain organization as determined for the eukaryotic Agos. In contrast, short pAgos variants contain the MID and PIWI domain only [5]. Recently, two studies have shed light on the biological role of bacterial Agos [8,9]. Together with our findings on the substrate specificity of an archaeal Ago variant [10], these data point to a paradigm shift in the field, as the spectrum of Argonaute silencing activities now also includes DNA- or RNA-guided DNA interference in prokaryotic organisms.


A prokaryotic twist on argonaute function.

Willkomm S, Zander A, Gust A, Grohmann D - Life (Basel) (2015)

Overall architecture of Argonaute from the three domains of life. The domain composition (left) and structures (middle) of the bacterial (based on Thermus thermophilus, PDB: 3DLH), the archaeal (based on Pyrococcus furiosus, PDB: 1U04) and the eukaryotic (based on human Argonaute 2, PDB: 4EI3) Argonaute reveal an evolutionarily conserved architecture. Differences can be found in the surface charge distribution of Argonaute proteins (negatively-charged surfaces in red; positively-charged surfaces in blue). The binding pocket for the 5'-end of the guide in the MID domain is highlighted with a green circle.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390867&req=5

life-05-00538-f001: Overall architecture of Argonaute from the three domains of life. The domain composition (left) and structures (middle) of the bacterial (based on Thermus thermophilus, PDB: 3DLH), the archaeal (based on Pyrococcus furiosus, PDB: 1U04) and the eukaryotic (based on human Argonaute 2, PDB: 4EI3) Argonaute reveal an evolutionarily conserved architecture. Differences can be found in the surface charge distribution of Argonaute proteins (negatively-charged surfaces in red; positively-charged surfaces in blue). The binding pocket for the 5'-end of the guide in the MID domain is highlighted with a green circle.
Mentions: The Argonaute (Ago) protein family was initially discovered in eukaryotes [1,2], but orthologs were found in many archaeal and bacterial organisms [3,4,5]. In eukaryotic organisms, Argonaute represents the principal component of the RNA silencing machinery. Despite the advancements in the understanding of Argonaute function in the eukaryotic field, the biological role of prokaryotic Argonaute proteins (pAgo) remained unknown for a long time. Argonaute proteins are encoded in ~32% and 9% of the sequenced archaeal and bacterial genomes, respectively [6]. PAgos were found to cluster in two groups distinguished by the presence or absence of the PAZ domain [5]. A lack of the PAZ domain often coincides with an apparent inactivation of the nuclease activity [5,6]. Interestingly, pAgos are often found in operons with a diverse range of endonucleolytic DNases (nucleases of the restriction endonuclease fold, a distinctive Sirtuin family domain or TIR domain proteins) and/or helicases (e.g., of the DinG-class) [3,5,7], leading to the hypothesis that the co-action of pAgo and an endo-DNase might act as a plasmid/phage restriction system. However, the subset of pAgos that exhibit a high sequence similarity to their eukaryotic counterpart does not seem to show conserved operonic associations with any other genes. Ago is composed of the N-terminal, PAZ (Piwi-Argonaute-Zwille), middle (MID) and PIWI (P-element-induced wimpy testis) domains interconnected by two structured linker regions (Figure 1 and Figure 2). This review mainly discusses the “long” pAgo variants, which share a comparable domain organization as determined for the eukaryotic Agos. In contrast, short pAgos variants contain the MID and PIWI domain only [5]. Recently, two studies have shed light on the biological role of bacterial Agos [8,9]. Together with our findings on the substrate specificity of an archaeal Ago variant [10], these data point to a paradigm shift in the field, as the spectrum of Argonaute silencing activities now also includes DNA- or RNA-guided DNA interference in prokaryotic organisms.

Bottom Line: Argonaute proteins can be found in all three domains of life.Despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic Argonaute proteins, the biological function of bacterial and archaeal Argonautes has remained elusive.We especially focus on archaeal Argonautes when discussing the details of the structural and dynamic features in Argonaute that promote substrate recognition and cleavage, thereby revealing differences and similarities in Argonaute biology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, Universitätsklinikum Schleswig-Holstein, University of Lübeck, 23538 Lübeck, Germany. willkomm@imm.uni-luebeck.de.

ABSTRACT
Argonaute proteins can be found in all three domains of life. In eukaryotic organisms, Argonaute is, as the functional core of the RNA-silencing machinery, critically involved in the regulation of gene expression. Despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic Argonaute proteins, the biological function of bacterial and archaeal Argonautes has remained elusive. This review discusses new findings in the field that shed light on the structure and function of Argonaute. We especially focus on archaeal Argonautes when discussing the details of the structural and dynamic features in Argonaute that promote substrate recognition and cleavage, thereby revealing differences and similarities in Argonaute biology.

No MeSH data available.