Origin of eukaryotic-like Vps23 shapes an ancient functional interplay between ESCRT and ubiquitin system in Asgard archaea

Functional interplay between the endosomal sorting complexes required for transport (ESCRT) and ubiquitin system underlies the ubiquitin-dependent sorting pathway, a specific trait of eukaryotic endomembrane system. Yet, its evolutionary origin remains unclear. Here, we show that a novel UEV-Vps23 family protein, that contains UEV and Vps23 domains, mediates an ancient ESCRT and ubiquitin system interplay in Asgard archaea. The UEV binds ubiquitin with high-affinity, making the UEV-Vps23 a sensor for sorting ubiquitinated cargo. A steadiness box in the Vps23 domain undergoes ubiquitination through a eukaryotic-like Asgard E1, E2, and RING E3 cascade. The UEV-Vps23 can switch between autoinhibited and active forms, by which likely regulates the ESCRT and ubiquitin system interplay. Furthermore, the shared sequence and structural homology among the UEV-Vps23, eukaryotic Vps23 and archaeal CdvA, implying that these proteins share a common evolutionary origin. Together, this work presents evidence that the ESCRT and ubiquitin system interplay had arisen early in Asgard evolution, antedating emergence of endomembrane system in eukaryogenesis. TeaserThe ESCRT and ubiquitin system interplay, a specific trait of eukaryotic endomembrane system, likely inherited from an Asgard archaeal ancestor.