A journey in time to the emergence of eukaryotic cells over 1.5 billion years ago

Prof. Natalie Elia and her colleagues from Ben-Gurion University of the Negev and Germany have demonstrated the communalities of ESCRT systems across all domains of life and illuminated a potential role of Asgard ESCRTs in the emergence of eukaryotic cells over 1.5 billion years ago.

Their findings were just published in The EMBO Journal.

The recently discovered archaeal Asgard superphylum is considered 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 eukaryogenesis, however, the properties and functions of these proteins are as yet mostly unresolved.

Proteins of the ESCRT membrane remodeling machine are among these ESPs, which are of particular interest because they are known to mediate basic cellular functions including cell division, vesicle release and nuclear membrane reformation, and are encoded by all life forms.

"In this study, we set out to understand the function of ESCRT proteins encoded by Asgard archaea. Notably, so far only two Asgard archaeal species have been isolated and there are no molecular tools that allow for studying these proteins in their physiological environment," explains Prof. Elia.

In an article entitled, "The Asgard archaeal ESCRT-III system forms helical filaments remodels eukaryotic-like membranes” they provide the first evidence that Asgard-ESCRTs assemble into filaments that are structurally and functionally related to their eukaryotic ESCRT homologs. Most importantly they showed that these ancient archaeal proteins can bend membranes of eukaryotic cells. Together these findings suggest that these proteins could potentially mediate the transition between prokaryotic and eukaryotic cells — a moment in evolutionary history that ultimately paved the way for the diversity of life forms, including humans.

The main findings of the study were:

1. Showing that Asgard ESCRTs assemble into helical filaments that resemble those of their eukaryotic homologs.
2. Resolving the first structure of the archaeal ESCRT-III complex and showing that the Asgard ESCRT-III polymer share similar properties with both prokaryotic and eukaryotic ESCRT-III polymers, supporting the phylogeny-based models that contend the Asgard-ESCRT system is an intermediate between the prokaryotic and eukaryotic ESCRT systems.
3. Demonstrating that Asgard-ESCRT proteins can remodel eukaryotic-like membranes, which are fundamentally different from archaeal membranes, suggesting a role for the ESCRT system in bridging the gap between prokaryotic and eukaryotic cells.
4. Showing that Asgard-ESCRT filaments rely on DNA for their organization into filaments and that DNA regulates their membrane remodeling capabilities, suggesting intimate relationships between ESCRTs, membranes, and DNA that can potentially explain the formation of the nuclear endomembrane during eukaryogenesis and/or cell division in the ancient world.

Prof. Elia is a member of the Department of Life Sciences in the Faculty of Natural Sciences.

This work was done in collaboration with the Bernheim-Groswasser and Sachse labs. Additional researchers included: Nataly Melnikov, Benedikt Junglas, Gal Halbi, Dikla Nachmias, Erez Zerbib, Noam Guetta, Alexander Upcher, Ran Zalk, Carsten Sachse, and Ann Bernheim-Groswasser.

The research was supported by a DFG (The Deutsche Forschungsgemeinschaft) grant through the DIP Program, and the Israel Science Foundation (Grant No. 1436/23).