Iyer, L., Burroughs, A.M. & Aravind, L. The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like beta-grasp domains. Genome Biol. 7, R60

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Genome biology (Impact Factor: 10.81). 02/2006; 7(7):R60. DOI: 10.1186/gb-2006-7-7-r60
Source: PubMed


Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear.
We systematically analyzed prokaryotic Ub-related beta-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages.
These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes.

7 Reads
  • Source
    • "Although none of the analyzed bacterial genomes contained a complete Ub toolkit, many bacteria were found to possess signaling systems that employ JAB peptidases, and E1 and E2 enzymes akin to the ones acting in ubiquitination (Iyer et al. 2006; Hochstrasser 2009; Humbard et al. 2010). These bacterial homologs act in functional contexts unrelated to protein labeling, such as molybdopterin and thyamin biosynthesis (ThiF E1) and siderophora biosynthesis (JAB) (Iyer et al. 2006; Koonin 2006). We also found F-box, U-box, and DUB enzymes in a few genomes of obligate intracellular parasitic bacteria, such as Agrobacterium tumefaciens, Legionella pneumophila, Candidatus Amoebophilus asiaticus, or various Chlamydiae, probably as a result of independent horizontal gene transfer (HGT) events (Koonin et al. 2001; Spallek et al. 2009; Schmitz- Esser et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analysing the origin and evolution of the ubiquitin signalling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole ubiquitin, SUMO and Ufm1 signalling networks by analysing representatives from all major eukaryotic, bacterial and archaeal lineages. We found that the ubiquitin toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic ubiquitin toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the ubiquitin-related genes, including the SUMO and Ufm1 ubiquitin-like systems. Ubiquitin and SUMO signalling further expanded during eukaryotic evolution, especially labelling and de-labelling enzymes responsible for substrate selection. Additionally, we analysed protein domain architecture evolution and found that multicellular lineages have the most complex ubiquitin systems in terms of domain architectures. Together, we demonstrate that the ubiquitin system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex post-translational regulation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Molecular Biology and Evolution 11/2014; DOI:10.1093/molbev/msu334 · 9.11 Impact Factor
  • Source
    • "Bacterial Ubls (MoaD and ThiS) are adenylated by cognate E1 homologs (MoeB and ThiF), subsequently bind activated sulfur via their C-termini to form thiocarboxylates, and finally act as sulfur donors (Figure 2; Pitterle and Rajagopalan, 1993; Taylor et al., 1998; Lauhon and Kambampati, 2000; Leimkühler et al., 2001; Zhang et al., 2010). These findings imply an evolutionary link between the eukaryotic Ub/Ubl system and the bacterial sulfur-transfer reaction (Iyer et al., 2006; Hochstrasser, 2009). Urm1 is an ubiquitin-related modifier and Uba4 is an E1-like enzyme involved in protein urmylation in eukaryotes (Furukawa et al., 2000; Figure 3B). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sulfur is an essential element for a variety of cellular constituents in all living organisms. In tRNA molecules, there are many sulfur-containing nucleosides, such as the derivatives of 2-thiouridine (s(2)U), 4-thiouridine (s(4)U), 2-thiocytidine (s(2)C), and 2-methylthioadenosine (ms(2)A). Earlier studies established the functions of these modifications for accurate and efficient translation, including proper recognition of the codons in mRNA or stabilization of tRNA structure. In many cases, the biosynthesis of these sulfur modifications starts with cysteine desulfurases, which catalyze the generation of persulfide (an activated form of sulfur) from cysteine. Many sulfur-carrier proteins are responsible for delivering this activated sulfur to each biosynthesis pathway. Finally, specific "modification enzymes" activate target tRNAs and then incorporate sulfur atoms. Intriguingly, the biosynthesis of 2-thiouridine in all domains of life is functionally and evolutionarily related to the ubiquitin-like post-translational modification system of cellular proteins in eukaryotes. This review summarizes the recent characterization of the biosynthesis of sulfur modifications in tRNA and the novel roles of this modification in cellular functions in various model organisms, with a special emphasis on 2-thiouridine derivatives. Each biosynthesis pathway of sulfur-containing molecules is mutually modulated via sulfur trafficking, and 2-thiouridine and codon usage bias have been proposed to control the translation of specific genes.
    Frontiers in Genetics 04/2014; 5:67. DOI:10.3389/fgene.2014.00067
  • Source
    • "The similarities suggest that all Ubls might have a common ancestor. Furthermore, small proteins with the β-grasp fold and C-terminal diglycine motif are widespread among prokaryotes and archaea67, providing additional evidence for the existence of a common ancestor of Ubls. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ubiquitin-like proteins play important roles in diverse biological processes. In this study, we present an unexpected finding that a ubiquitin-like small archaeal modifier protein (SAMP2) from Haloferax volcanii adopts two distinct states under low ionic condition. One of these is similar to the β-grasp structure conserved in ubiquitin-like proteins from eukaryotes; the other is disordered, like prokaryotic ubiquitin-like protein, Pup. Furthermore, our study reveals that the conformation of SAMP2 is dependent on ionic strength. With the increase of ion concentration, SAMP2 undergoes a conformational conversion from disorder to order, indicating that the ordered conformation is the functional form of SAMP2 under the physiological condition of H. volcanii.
    Scientific Reports 07/2013; 3:2136. DOI:10.1038/srep02136 · 5.58 Impact Factor
Show more

Preview (4 Sources)

7 Reads
Available from