The emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The endosomal sorting complex required for transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes. However, structural and functional features of Asgard ESCRT remain uncharacterized. Here, we show that Vps4, Vps2/24/46, and Vps20/32/60, the core functional components of the Asgard ESCRT, coevolved eukaryote-like structural and functional features. Phylogenetic analysis shows that Asgard Vps4, Vps2/24/46, and Vps20/32/60 are closely related to their eukaryotic counterparts. Molecular dynamics simulation and biochemical assays indicate that Asgard Vps4 contains a eukaryote-like microtubule-interacting and transport (MIT) domain that binds the distinct type 1 MIT-interacting motif and type 2 MIT-interacting motif in Vps2/24/46 and Vps20/32/60, respectively. The Asgard Vps4 partly, but much more efficiently than homologs from other archaea, complements the vps4 null mutant of Saccharomyces cerevisiae, further supporting the functional similarity between the membrane remodeling machineries of Asgard archaea and eukaryotes. Thus, this work provides evidence that the ESCRT complexes from Asgard archaea and eukaryotes are evolutionarily related and functionally similar. Thus, despite the apparent absence of endomembranes in Asgard archaea, the eukaryotic ESCRT seems to have been directly inherited from an Asgard ancestor, to become a key component of the emerging endomembrane system.

中文翻译：

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在Asgard古细菌中真核生物样Vps4和ESCRT-III亚基的共同进化。

内膜系统的出现是真核生物发生过程中细胞复杂性演变的关键步骤。运输（ESCRT）机械所需的内体分选复合物对于真核细胞内膜系统功能至关重要，也是必需的。最近，已经在新提出的古细菌超级菌种Asgard古细菌的基因组中鉴定出编码真核生物样ESCRT蛋白成分的基因，该基因被认为包括最接近的真核生物现存亲属。但是，Asgard ESCRT的结构和功能特征仍未表征。在这里，我们显示了Asgard ESCRT的核心功能组件Vps4，Vps2 / 24/46和Vps20 / 32/60共同进化了类似真核生物的结构和功能特征。系统发育分析表明，Asgard Vps4，Vps2 / 24/46，Vps20 / 32/60和Vps20 / 32/60与它们的真核对应物密切相关。分子动力学模拟和生化分析表明，Asgard Vps4包含一个真核生物样微管相互作用和转运（MIT）结构域，该结构域结合了Vps2 / 24/46和Vps20 /中不同的1型MIT相互作用基序和2型MIT相互作用基序。 32/60。Asgard Vps4的一部分，但比其他古细菌的同系物效率更高，对vps4酿酒酵母的无效突变体，进一步支持了Asgard古生菌和真核生物的膜重塑机制之间的功能相似性。因此，这项工作提供了证据，证明来自Asgard古细菌和真核生物的ESCRT复合物在进化上相关且在功能上相似。因此，尽管阿斯加德古细菌中显然没有内膜，但真核ESCRT似乎是直接从阿斯加德祖先继承而来的，成为新兴的内膜系统的重要组成部分。