Heimdallarchaea encodes profilin with eukaryotic-like actin regulation and polyproline binding

Sabeen Survery, Fredrik Hurtig, Syed Razaul Haq, Ann-Christin Lindås, Celestine N. Chi

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29th April 20

The evolutionary events which led to the first eukaryotic cell are still controversial1-4. The Asgard genome encodes a variety of eukaryotic signature proteins previously unseen in prokaryotes. Functional and structural characterization of these proteins is beginning to shed light on the complexity and pedigree of the ancestral eukaryotic cell5,6. In eukaryotes, the key cytoskeletal protein actin is important for diverse cellular processes such as membrane remodeling and cell motility7. Dynamic polymerization of actin provides both structure and generates the force which drives motility and membrane remodeling. These processes demand rapid filament assembly and disassembly on microsecond timescales. In eukaryotes, a variety of highly adapted proteins including gelsolin, profilin, VASP, ARP2/3 and signaling molecules (Phosphatidylinositol-4,5-bisphosphate (PIP2)) are crucial for organizing cellular cytoskeleton dynamics. Amongst others, the Asgard genomes encode predicted putative profilin homologues that regulate eukaryotic actin polymerization in vitro5,8. Interestingly, Asgard profilins appear to be regulated by PIP2, but not by polyproline rich motifs which are important for recruitment of actin:profilin complexes in eukaryotes5,9. These findings indicate that the Asgard archaea may have possessed analogous membrane organization to present-day eukaryotes, but that polyproline-mediated profilin regulation may have emerge later in the eukaryotic lineage5. Here, we show that Heimdallarchaeota, a candidate phylum within the Asgard superphylum, encodes a putative profilin (heimProfilin) that interacts with PIP2 and is regulated by polyproline motifs, implicative of an origin predating the rise of the eukaryotes. Additionally, we provide evidence for a novel regulatory mechanism whereby an extended N-terminal loop abolishes PIP2 and polyproline interactions. Lastly, we provide the first evidence for actin polymerization of an Asgard actin homologue. In context, these findings provide further evidence for the existence of a complex cytoskeleton already in last eukaryotic common ancestor (LECA).

1       Spang, A. et al. Asgard archaea are the closest prokaryotic relatives of eukaryotes. PLoS Genet 14, e1007080, doi:10.1371/journal.pgen.1007080 (2018).

2       Da Cunha, V., Gaia, M., Gadelle, D., Nasir, A. & Forterre, P. Lokiarchaea are close relatives of Euryarchaeota, not bridging the gap between prokaryotes and eukaryotes. PLoS Genet 13, e1006810, doi:10.1371/journal.pgen.1006810 (2017).

3       Lopez-Garcia, P. & Moreira, D. Open Questions on the Origin of Eukaryotes. Trends Ecol Evol 30, 697-708, doi:10.1016/j.tree.2015.09.005 (2015).

4       Koonin, E. V. Origin of eukaryotes from within archaea, archaeal eukaryome and bursts of gene gain: eukaryogenesis just made easier? Philos Trans R Soc Lond B Biol Sci370, 20140333, doi:10.1098/rstb.2014.0333 (2015).

5       Akil, C. & Robinson, R. C. Genomes of Asgard archaea encode profilins that regulate actin. Nature 562, 439-443, doi:10.1038/s41586-018-0548-6 (2018).

6       Imachi, H. et al. Isolation of an archaeon at the prokaryote-eukaryote interface. Nature577, 519-525, doi:10.1038/s41586-019-1916-6 (2020).

7       Pollard, T. D. Actin and Actin-Binding Proteins. Cold Spring Harb Perspect Biol 8, doi:10.1101/cshperspect.a018226 (2016).

8       Zaremba-Niedzwiedzka, K. et al. Asgard archaea illuminate the origin of eukaryotic cellular complexity. Nature 541, 353-358, doi:10.1038/nature21031 (2017).

9       Reinhard, M. et al. The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins. EMBO J 14, 1583-1589 (1995).

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


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