Abstract
In eukaryotes, the covalent attachment of ubiquitin chains directs substrates to the proteasome for degradation. Recently, ubiquitin-like modifications have also been described in the archaeal domain of life. It has subsequently been hypothesized that ubiquitin-like proteasomal degradation might also operate in these microbes, since all archaeal species utilize homologues of the eukaryotic proteasome. Here we perform a structural and biochemical analysis of a ubiquitin-like modification pathway in the archaeon Sulfolobus acidocaldarius. We reveal that this modifier is homologous to the eukaryotic ubiquitin-related modifier Urm1, considered to be a close evolutionary relative of the progenitor of all ubiquitin-like proteins. Furthermore we demonstrate that urmylated substrates are recognized and processed by the archaeal proteasome, by virtue of a direct interaction with the modifier. Thus, the regulation of protein stability by Urm1 and the proteasome in archaea is likely representative of an ancient pathway from which eukaryotic ubiquitin-mediated proteolysis has evolved.
Highlights
In eukaryotes, the covalent attachment of ubiquitin chains directs substrates to the proteasome for degradation
We initially searched for eukaryotic-like Ub and ubiquitin-like proteins (Ubls) homologues in the genomes of the thermophilic archaea S. acidocaldarius and S. solfataricus
Since the discovery of the SAMP family of proteins in the archaea[27], these ancestral Ubls have been implicated in proteasomal processing pathways equivalent to the eukaryotic ubiquitin-proteasome system
Summary
The covalent attachment of ubiquitin chains directs substrates to the proteasome for degradation. The discovery of an unanticipated structural homology between the bacterial sulphur-transfer proteins ThiS and MoaD, and the eukaryotic Ub/Ubl proteins[8,9] led to speculation that primitive prokaryotic homologues are the antecedents of the eukaryotic Ub/Ubl family[10] These prokaryotic ubiquitin-like homologues share the characteristic Ub/Ubl-like b-grasp structural fold[11,12,13], and are activated with similar catalytic chemistry to Ub/Ubls[10]. Urm[1] mediates sulphur mobilization reactions during post-translational tRNA modification reactions[25,26] This functional duality led to further speculation that some prokaryotic sulphur-transfer Ubl homologues might play roles in substrate conjugation. Identified in the halophilic archaeon H. volcanii, bioinformatic analyses have since indicated that SAMPs are widely distributed across all the archaeal kingdoms[33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
