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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eukaryotic ubiquitin-like proteins (UBLs) have evolved from prokaryotic sulfur-carrier proteins (SCPs). Ubiquitin related modifier 1 (Urm1) shares biochemical and structural features of UBLs and SCPs and is essential for 2-thiolation of cytoplasmic tRNA. This chemical modification of wobble uridine is highly conserved amongst species and is achieved via Urm1 thiocarboxylation by the non-canonical ubiquitin activating 4 enzyme (Uba4), which contains an E1- and a Rhodanese (RHD) domain. While the RHD catalyzes the last step in Urm1-thiocarboxylate formation, the previous steps in Urm1 activation and the interplay between the two domains have remained elusive. To define the underlying mechanism, we established an Urm1 in vitro thiocarboxylation assay, which combined with structure-function and chemical profiling analyses revealed a critical thioester linkage between Urm1 and Uba4 residue Cys225. This linkage is indispensable for the Urm1 intramolecular transfer between the two domains of Uba4 and it is thus, essential for tRNA thiolation in vivo. These findings contribute to a deeper understanding of UBL evolution.
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PMID:The Uba4 domain interplay is mediated via a thioester that is critical for tRNA thiolation through Urm1 thiocarboxylation. 2971 31

Ubiquitin-like protein (Ubl) modification targets proteins for transient inactivation and/or proteasome-mediated degradation in archaea. Here the rhodanese-like domain (RHD) protein UbaC (HVO_1947) was found to copurify with the E1-like enzyme (UbaA) of the Ubl modification machinery in the archaeon Haloferax volcanii UbaC was shown to be important for Ubl ligation, particularly for the attachment of the Ubl SAMP2/3s to protein targets after exposure to oxidants (NaOCl, dimethyl sulfoxide [DMSO], and methionine sulfoxide [MetO]) and the proteasome inhibitor bortezomib. While UbaC was needed for ligation of the Ubl SAMP1 to MoaE (the large subunit of molybdopterin synthase), it was not important in the formation of oxidant-induced SAMP1 protein conjugates. Indicative of defects in sulfur relay, mutation of ubaC impaired molybdenum cofactor (Moco)-dependent DMSO reductase activity and cell survival at elevated temperature, suggesting a correlation with defects in the 2-thiolated state of wobble uridine tRNA. Overall, the archaeal stand-alone RHD UbaC has an important function in Ubl ligation and is associated with sulfur relay processes.IMPORTANCE Canonical E2 Ub/Ubl-conjugating enzymes are not conserved in the dual-function Ubl systems associated with protein modification and sulfur relay. Instead, the C-terminal RHDs of E1-RHD fusion proteins are the apparent E2 modules of these systems in eukaryotes. E1s that lack an RHD are common in archaea. Here we identified an RHD (UbaC) that serves as an apparent E2 analog with the E1-like UbaA in the dual-function Ubl sampylation system of archaea. Unlike the eukaryotic E1-RHD fusion, the archaeal RHD is a stand-alone protein. This new insight suggests that E1 function in Ubl pathways could be influenced by shifts in RHD abundance and/or competition with other protein partners in the cell.
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PMID:Rhodanese-Like Domain Protein UbaC and Its Role in Ubiquitin-Like Protein Modification and Sulfur Mobilization in Archaea. 3108 91