Abstract
The archaeal Asgard superphylum currently stands as the most promising prokaryotic candidate, from which eukaryotic cells emerged. This unique superphylum encodes for eukaryotic signature proteins (ESP) that could shed light on the origin of eukaryotes, but the properties and function of these proteins is largely unresolved. Here, we set to understand the function of an Asgard archaeal protein family, namely the ESCRT machinery, that is conserved across all domains of life and executes basic cellular eukaryotic functions, including membrane constriction during cell division. We find that ESCRT proteins encoded in Loki archaea, express in mammalian and yeast cells, and that the Loki ESCRT-III protein, CHMP4-7, resides in the eukaryotic nucleus in both organisms. Moreover, Loki ESCRT-III proteins associated with chromatin, recruited their AAA-ATPase VPS4 counterpart to organize in discrete foci in the mammalian nucleus, and directly bind DNA. The human ESCRT-III protein, CHMP1B, exhibited similar nuclear properties and recruited both human and Asgard VPS4s to nuclear foci, indicating interspecies interactions. Mutation analysis revealed a role for the N terminal region of ESCRT-III in mediating these phenotypes in both human and Asgard ESCRTs. These findings suggest that ESCRT proteins hold chromatin binding properties that were highly preserved through the billion years of evolution separating Asgard archaea and humans. The conserved chromatin binding properties of the ESCRT membrane remodeling machinery, reported here, may have important implications for the origin of eukaryogenesis.
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Data availability
All raw data that support the findings of this study are available upon request from the corresponding author NE.
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Acknowledgements
We thank Dan Levi (BGU) and Eran Meshorer (HUJI) for fruitful discussions on chromatin-binding proteins and constructive advice. We thank Chen Keasar (BGU) for assistance with structure prediction measurements. We also thank, Dr. Ran Zalk (BGU) for helpful feedback and technical help with structural analysis. We thank all members of the Elia lab for critical feedback throughout the project. The Elia laboratory is funded by the Israeli Science Foundation (ISF) Grant no. 1323/18. I. M. acknowledges support from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant no. 640384) and the Israel Science Foundation (grant no. 1947/19).
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DN, IM, and NE conceptualized the project. DN designed, performed, and analyzed all cell biology and biochemical experiments. NM purified recombinant proteins. AZ performed phylogenetic analysis and generated density plot. MS performed experiments. MS ad RY performed and analyzed structure predictions. YD assisted in experiments. IT and AA assisted with experiments in yeast. BF and PS performed bioinformatics analysis of Asgard CHMP4-7 N-terminal regions. RZ generated structural model and helped with structural data interpretation. NE wrote the manuscript with the help of DN and IM. All authors read and revised the manuscript.
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Nachmias, D., Melnikov, N., Zorea, A. et al. Asgard ESCRT-III and VPS4 reveal conserved chromatin binding properties of the ESCRT machinery. ISME J 17, 117–129 (2023). https://doi.org/10.1038/s41396-022-01328-2
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DOI: https://doi.org/10.1038/s41396-022-01328-2
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