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The evolutionary journey of Argonaute proteins

Abstract

Argonaute proteins are conserved throughout all domains of life. Recently characterized prokaryotic Argonaute proteins (pAgos) participate in host defense by DNA interference, whereas eukaryotic Argonaute proteins (eAgos) control a wide range of processes by RNA interference. Here we review molecular mechanisms of guide and target binding by Argonaute proteins, and describe how the conformational changes induced by target binding lead to target cleavage. On the basis of structural comparisons and phylogenetic analyses of pAgos and eAgos, we reconstruct the evolutionary journey of the Argonaute proteins through the three domains of life and discuss how different structural features of pAgos and eAgos relate to their distinct physiological roles.

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Figure 1: Domain architectures of the PIWI superfamily proteins.
Figure 2: TtAgo with 21-mer guide DNA (binary complex) and with complementary 12-mer target RNA (ternary complex) adopt cleavage-incompatible conformations.
Figure 3: TtAgo with 5′-phosphorylated 21-mer guide DNA and complementary 15-mer and 19-mer target RNAs (ternary complex) adopt cleavage-compatible conformations.
Figure 4: Structure-based insights into the cleavage mechanism of TtAgo.
Figure 5: Structures of binary complexes of KpAgo and hAGO2 bound to 5′-phosphorylated guide RNAs.
Figure 6: Phylogenetic trees of Argonaute proteins.

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Acknowledgements

This work was financially supported by grants from the Netherlands Organization of Scientific Research (NWO) to J.v.d.O. (NWO-TOP, 845.10.003) and the US National Institutes of Health to D.J.P. (TR01 GM104962). K.M. and E.V.K. are supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). K.N. is supported by Precursory Research for Embryonic Science and Technology (PRESTO) from the Japan Science and Technology (JST) Agency.

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Supplementary Data 1

Sequence alignment of prokaryotic Argonautes. (DOCX 79 kb)

Supplementary Data 2

Complete phylogenetic tree of prokaryotic Argonautes. (PDF 4337 kb)

Supplementary Data 3

Sequence alignment of eukaryotic Argonautes. (DOCX 49 kb)

Supplementary Data 4

Complete phylogenetic tree of eukaryotic Argonautes. (PDF 1295 kb)

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Swarts, D., Makarova, K., Wang, Y. et al. The evolutionary journey of Argonaute proteins. Nat Struct Mol Biol 21, 743–753 (2014). https://doi.org/10.1038/nsmb.2879

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