Beschreibung:
<jats:p>Ubiquitin (Ub) conjugation in eukaryotes and ThiS thiocarboxylation in bacteria require their cognate activating enzyme, E1 and ThiF, respectively. Conversely in archaea, the E1/ThiF analog, UbaA is required for the conjugation of the Ub/ThiS‐like protein SAMP2 and in SAMP2‐mediated sulfur relay for tRNA thiolation. To further corroborate our current model about the role of UbaA at the crossroad of protein conjugation and sulfur transfer, we <jats:italic>in trans</jats:italic>‐express the human Ub and <jats:italic>E. coli</jats:italic> ThiS in the haloarchaeon <jats:italic>Haloferax volcanii.</jats:italic> Interestingly, both Ub and ThiS covalently linked onto archaeal cytosolic proteins in an UbaA‐dependent manner, demonstrating that UbaA has a broad specificity in activating Ub‐fold family of proteins. This substrate promiscuity supports our hypothesis that the mechanism of UbaA‐mediated SAMP2 activation in archaea provides an evolutionary link that differentiates isopeptide‐based conjugation shared among eukaryotes and sulfur mobilization shared among bacteria.</jats:p><jats:p><jats:bold><jats:italic>Grant Funding Source</jats:italic></jats:bold><jats:italic>: Supported by NIH</jats:italic></jats:p>