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Asgard ESCRT-IIIs assemble into helical filaments in the presence of DNA and remodel eukaryotic membranes

Melnikov, N.; Nachmias, D.; Halbi, G.; Upcher, A.; Zalk, R.; Bernheim, A.; Elia, N.

2022-09-08 biochemistry
10.1101/2022.09.07.506706 bioRxiv
Show abstract

The ESCRT machinery mediates membrane remodeling in numerous processes in cells including cell division and nuclear membrane reformation. The identification of ESCRT homologs in Asgard archaea, currently considered the closest ancestor of eukaryotes, implies a role for ESCRTs in the membrane remodeling processes that occurred during eukaryogenesis. Yet, the function of these distant ESCRT homologs is mostly unresolved. Here we show that Asgard ESCRT-III proteins of the Lokiarcheota self-assemble into helical filaments, a hallmark of the ESCRT system. We determined the cryo-EM structure of the filaments at 3.6 [A] resolution and found that they share features of bacterial and eukaryotic ESCRT-III assemblies. Markedly, Asgard ESCRT-III filaments bound and deformed eukaryotic-like membrane vesicles. Oligonucleotides facilitated the assembly of ESCRT-III filaments and tuned the extent of membrane remodeling. The ability of Asgard archaeal ESCRTs to remodel eukaryotic-like membranes, which are fundamentally different from archaeal membranes, and the structural properties of these proteins places them at the junction between prokaryotes and eukaryotes, substantiating a role for ESCRTs in eukaryogenesis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/506706v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@114999forg.highwire.dtl.DTLVardef@171a296org.highwire.dtl.DTLVardef@16931e0org.highwire.dtl.DTLVardef@1497c50_HPS_FORMAT_FIGEXP M_FIG C_FIG

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