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

Abstract

Summary: Functional interplay between the endosomal sorting complexes required for transport (ESCRT) and the ubiquitin system underlies the ubiquitin-dependent cargo-sorting pathway of the eukaryotic endomembrane system, yet its evolutionary origin remains unclear. Here, we show that a UEV-Vps23 protein family, which 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 an Asgard E1, E2, and RING E3 cascade. The UEV-Vps23 switches between autoinhibited and active forms, regulating the ESCRT and ubiquitin system interplay. Furthermore, the shared sequence and structural homology among the UEV-Vps23, eukaryotic Vps23, and archaeal CdvA suggest a common evolutionary origin. Together, this work expands our understanding of the ancient ESCRT and ubiquitin system interplay that likely arose antedating divergent evolution between Asgard archaea and eukaryotes.

Keywords

• CP: Microbiology
• CP: Cell biology