Comparison of Proteasomes Across Archaea Reveals Variation in 20S Subunit Composition and Conservation of Post-Translational Modifications

Abstract

Proteasomes are proteolytic complexes that regulate protein abundance and recycle damaged proteins. The 20S core particle is central to proteasome function and consists of 4 stacked, heptameric rings of α and β subunits in an α₇β₇β₇α₇ configuration that is conserved across Eukaryotes and Archaea. Despite this conservation, 20S core particles display substantial diversity in the types of α and β subunits that form the complex, with further variation introduced by post-translational modifications. In this study, we integrated publicly available 3D-structural data, AlphaFold models, genomic sequences, proteomic datasets and published findings to provide new insights into proteasome evolution, with a focus on the relationships of the 20S core particle among archaea. We found that post-translational modification sites are more conserved among α-type subunits than β-type subunits and that β-type subunit genes display a potentially high rate of horizontal gene transfer. We also discover an additional α-helix in an Asgard archaeon α1 protein of unknown function. Together, these findings highlight the evolutionary diversity of archaeal proteasomes through their conservation of post-translational modification sites and types of subunits.