Abstract
Urm1 (ubiquitin related modifier 1) is a molecular fossil in the class of ubiquitin-like proteins (UBLs). It encompasses characteristics of classical UBLs, such as ubiquitin or SUMO (small ubiquitin-related modifier), but also of bacterial sulfur-carrier proteins (SCP). Since its main function is to modify tRNA, Urm1 acts in a non-canonical manner. Uba4, the activating enzyme of Urm1, contains two domains: a classical E1-like domain (AD), which activates Urm1, and a rhodanese homology domain (RHD). This sulfurtransferase domain catalyzes the formation of a C-terminal thiocarboxylate on Urm1. Thiocarboxylated Urm1 is the sulfur donor for 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), a chemical nucleotide modification at the wobble position in tRNA. This thio-modification is conserved in all domains of life and optimizes translation. The absence of Urm1 increases stress sensitivity in yeast triggered by defects in protein homeostasis, a hallmark of neurological defects in higher organisms. In contrast, elevated levels of tRNA modifying enzymes promote the appearance of certain types of cancer and the formation of metastasis. Here, we summarize recent findings on the unique features that place Urm1 at the intersection of UBL and SCP and make Urm1 an excellent model for studying the evolution of protein conjugation and sulfur-carrier systems.
Highlights
Urm1 is a non-canonical ubiquitin-like protein (UBL).Classical ubiquitin-like proteins (UBLs), like ubiquitin, SUMO or Nedd8, are conjugated to target proteins following an intricate enzymatic cascade
UBLs are adenylated at their conserved C-terminal diglycine motif by a dedicated activating enzyme (E1)
The bacterial MoaD and ThiS were chosen in the query to search for distantly related ubiquitin-like conjugation systems [1,2]
Summary
Urm (ubiquitin related modifier 1) is a non-canonical ubiquitin-like protein (UBL). Classical UBLs, like ubiquitin, SUMO (small ubiquitin-related modifier) or Nedd, are conjugated to target proteins following an intricate enzymatic cascade. Bacterial sulfur-carrier protein (SCP) systems share an identical activating mechanism with UBLs. The bacterial MoaD (molybdopterin synthase sulfur carrier subunit) and ThiS (thiamin biosynthesis protein) were chosen in the query to search for distantly related ubiquitin-like conjugation systems [1,2]. Despite the low similarity of the primary sequence, these proteins all share β-grasp fold, consisting of five β-sheets arranged around a central helix. The SAMP-activating enzyme UbaA is critical for protein tion as well as sulfur mobilization during tRNAduring thiolation andthiolation molybdopterin biosynthesis. We summarize recent insights intonon-canonical the role of Urm asfeatures the sulfur in tRNA thio-modification and compare the unique. Urm in thio-modification to tRNA other UBLs and SCPs. and compare the unique non-canonical UBL features of Urm to other UBLs and SCPs
Sign-in/Register to view highlights & summary 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.
