Asgard ESCRT-III and VPS4 reveal evolutionary conserved chromatin binding properties of the ESCRT machinery

Abstract

The ESCRT machinery drive membrane remodeling in numerous processes in eukaryotes. Genes encoding for ESCRT proteins have been identified in Asgard archaea, a newly discovered superphylum, currently recognized as the ancestor of all eukaryotes. This begs the question of the functional evolutionary origin of this machinery and its conservation across lineages. Here, we find that Asgard-ESCRT’s exhibit conserved DNA-binding properties, which is derived from recruitment of specific members. We show that Asgard-ESCRT-III/VPS4 homologs interact with one another inside mammalian cells, associate with chromatin, and recruit their counterparts to organize in discrete foci in the mammalian nucleus. This is congruent with human-ESCRT-III homologs. We find that human- and Asgard-ESCRT-IIIs associate with chromatin via the same N terminal domain, and that human-ESCRT-III can recruit Asgard-VPS4 to the nucleus to form foci. Therefore, ESCRTs possess chromatin binding properties that were preserved through the billion years of evolution that separate Asgard and human cells.

Tracing back variations in archaeal ESCRT-based cell division to protein domain architectures

“…In Euryarchaeota, some few species show CdvB and/or CdvC proteins encoded in their genome, but most species do not possess Cdv proteins. In Asgard archaea, only little is known, because it was just recently possible to cultivate a member of this super-phylum [ 5 , 12 ], but metagenome data and protein prediction indicates that genes encoding for CdvB and CdvC proteins are common within this group, and first experimental evidence is accumulating [ 13 , 14 ]. In TACK archaea, to which Sulfolobus acidocaldarius belongs, species of all groups except Thermoproteales possess all three proteins CdvABC.…”

The Asgard archaeal ESCRT-III system forms helical filaments and remodels eukaryotic membranes, shedding light on the emergence of eukaryogenesis

“…Eukaryotic ESCRT-III proteins polymerize into helical filaments - a hallmark of ESCRT- III organization that is thought to be essential for their function in membrane remodeling (8, 28). Polymerization is mediated by the snf7 domain that is conserved in both archaea and eukaryotes, but the polymerization properties of Asgard ESCRT-III has not been examined (5, 20, 26). To investigate the assembly properties of Asgard ESCRT-III proteins, we purified recombinant versions of the ESCRT-III proteins CHMP4-7 and CHMP 1-3, encoded by the Loki GC14_75 strain (KKK44605.1 and KKK42122.1, respectively).…”

“…In this respect, mammalian ESCRT-III proteins have been shown to mediate sealing of the nuclear membrane post cell division and to regulate the attachment of heterochromatin to the newly formed nuclear envelop (33-35). Moreover, we recently reported that Loki CHMP 4-7 is targeted to the nucleus when over expressed in eukaryotic cells (26). Finally, the membrane binding experiments performed here were done using eukaryotic-like phospholipids, which are fundamentally different from archaeal lipids but may resemble the lipid composition of the newly formed nuclear membrane.…”

“…Additionally, the sequence of Asgard ESCRT-III/VPS4 proteins is more closely related to those of eukaryotes than to other archaeal ESCRT systems (the CDV system) (5, 20). Lastly, VPS4 homologs of Asgard archaea were shown to functionally interact with eukaryotic ESCRTs in both yeast and mammalian cells (5, 26). Notably, the Asgard ESCRT-III subfamily is substantially reduced compared to eukaryotes with only two ESCRT-III proteins (named here CHMP1-3 and CHMP4-7) encoded in some species including Loki and Heimdall archaeota (1, 5, 7, 26).…”

“…Lastly, VPS4 homologs of Asgard archaea were shown to functionally interact with eukaryotic ESCRTs in both yeast and mammalian cells (5, 26). Notably, the Asgard ESCRT-III subfamily is substantially reduced compared to eukaryotes with only two ESCRT-III proteins (named here CHMP1-3 and CHMP4-7) encoded in some species including Loki and Heimdall archaeota (1, 5, 7, 26). Hence, the Asgard ESCRT system constitutes a minimalist ESCRT machinery that may hold the core capabilities of eukaryotic ESCRTs and could have been involved in membrane remodelling processes that occurred during eukaryogenesis.…”