Prokaryotic ubiquitin-like protein

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Pup-like protein family
Pup-prokaryotic ubiquitin-like protein.png
Three Prokaryotic ubiquitin-like proteins (blue) bound to proteasomal ATPase Mpa (red
Identifiers
SymbolPup
Pfam PF05639
InterPro IPR008515

Prokaryotic ubiquitin-like protein (Pup) is a functional analog of ubiquitin found in the prokaryote Mycobacterium tuberculosis . [1] Like ubiquitin, Pup serves to direct proteins to the proteasome for degradation in the Pup-proteasome system (PPS). However, the enzymology of ubiquitylation and pupylation is different, owing to their distinct evolutionary origins. In contrast to the three-step reaction of ubiquitylation, pupylation requires only two steps, and thus only two enzymes are involved in pupylation. The enzymes involved in pupylation are descended from glutamine synthetase.[ citation needed ]

Contents

Similar to ubiquitin, Pup is attached to specific lysine residues of substrate proteins by isopeptide bonds; this is called pupylation. It is then recognized by the protein Mycobacterium proteasomal ATPase (Mpa), in a mechanism that induces folding of Pup. [2] Mpa delivers the substrate protein to the proteasome for degradation by coupling of ATP hydrolysis.

The discovery of Pup indicates that like eukaryotes, bacteria may use a small-protein modifier to control protein stability.

The Pup gene encodes a 64–amino acid protein with a molecular size of about 6.9 kDa. [3]

Pup is an intrinsically disordered protein. [4] In 2010, scientists at the Brookhaven National Laboratory determined the X-ray crystal structure of the complex between Pup and its delivery enzyme Mpa 3M9D ​ and found that Pup binding to Mpa induces the folding of a unique alpha-helix. [2]

In 2017, the presence of Pup homologs in bacterial species outside of the group of gram-positive bacteria was reported. [5] The Pup homologs were termed UBact (for Ubiquitin Bacterial), although the distinction has not been proven to be phylogenetically supported by a separate evolutionary origin and is without experimental evidence. [5] UBact is a homolog of Pup, and is found in several phyla of gram-negative bacteria (Pup is found predominantly in the gram-positive bacterial phylum Actinomycetota).

Ubiquitin bacterial

Prokaryotic ubiquitin-like protein
Identifiers
SymbolUBact
InterPro IPR037543
Figure 1. A diagram of the UBact Pup homolog. Phyre2 server was used to predict the structure of the UBact Pup homolog from the bacterium Methylacidiphilum infernorum. Given the similarity to Pup, the prediction of a structure is doubtful, as Pup is proven to be instrinsically disordered in solution (see text for references). UBact family.png
Figure 1. A diagram of the UBact Pup homolog. Phyre2 server was used to predict the structure of the UBact Pup homolog from the bacterium Methylacidiphilum infernorum. Given the similarity to Pup, the prediction of a structure is doubtful, as Pup is proven to be instrinsically disordered in solution (see text for references).

Ubiquitin Bacterial (UBact) is a protein that is homologous to Prokaryotic ubiquitin-like protein (Pup). UBact was recently described by the group of Professor Aaron Ciechanover at the Technion, Israel. [5]

Ubiquitin was named for its ubiquitous presence among eukaryotes, while UBact ('Ubiquitin bacterial') is very limited in occurrence among the vast number of bacterial species. [5] The terms 'Ubiquitin Bacterial' and 'Prokaryotic ubiquitin-like protein' suggest a molecular similarity between ubiquitin and UBact/Pup which is largely absent. [6] While ubiquitin assumes a highly stable three-dimensional structure in solution, [7] Pup has been shown to belong to the group of intrinsically disordered proteins. [8] [9]

The establishment of the term UBact is controversial, since to date there is no experimental evidence presented to justify the distinction of UBact from Pup. [5] The term UBact was denoted because several bacterial species from the phylum Nitrospirae (where UBact was initially identified; e.g., Leptospirillum ferriphilum ) contain both the Pup-proteasome system [10] and a novel ORF-proteasome system that needed to be addressed [11] and therefore was denoted UBact. [5] The conjugation-proteasome components neighboring the UBact and Pup loci in these Nitrospirae bacteria show weak similarity and are probably not entirely redundant. Figure 2 illustrates the differences between the UBact and Pup loci in the representative Nitrospirae bacterium Leptospirillum ferrodiazotrophum. Further analyses of the UBact (and not Pup) locus in Leptospirillum ferrodiazotrophum revealed its existence and extreme conservation across several gram-negative bacterial phyla, as illustrated in figure 3.

Figure 2. Alignment of UBact (EES53751) and Pup (EES52728) from the bacterium Leptospirillum ferrodiazotrophum to assess their similarity. Alignment of UBact and Pup from the bacterium Leptospirillum ferrodiazotrophum.png
Figure 2. Alignment of UBact (EES53751) and Pup (EES52728) from the bacterium Leptospirillum ferrodiazotrophum to assess their similarity.
Figure 3. Demonstration of UBact C-terminus conservation across tremendous evolutionary distance. Alignment of UBact from several bactrerial phyla.png
Figure 3. Demonstration of UBact C-terminus conservation across tremendous evolutionary distance.

In spite of the large difference in sequence, UBact is homologous to Pup and shares several characteristics with it: (i) same genomic location within a cluster of genes homologous to Mpa -> Dop -> Pup/UBact -> PrcB -> PrcA -> PafA, (ii) C-terminal sequence that ends exclusively with glutamine or glutamate across bacterial species, (iii) short size (similar to that of ubiquitin) and, (iv) high sequence conservation across tremendous evolutionary distance (a characteristic also in common with ubiquitin). The differences between UBact and Pup are their taxonomic distribution and amino acid sequences. While Pup is predominantly found in the gram-positive phylum Actinomycetota, UBact was identified only in gram-negative bacteria from the following five phyla: Nitrospirota, Verrucomicrobiota, Armatimonadota, Nitrospinota, and Planctomycetota. UBact was also identified in the genomes of several candidatus bacteria, and specifically from the candidate divisions "Acetothermia", "Handelsmanbacteria", "Fraserbacteria", "Terrybacteria", "Poribacteria", "Parcubacteria", and "Yanofskybacteria". [5] With regard to the amino acid sequence, in difference from Pup and Ubiquitin, UBact does not contain a di-glycine motif at its C-terminus. Rather, it usually ends with the sequence R[T/S]G[E/Q] (see figure 3).

It took almost ten years since the discovery of Pup in 2008, [1] to identify UBact. This is probably due to the difference between Pup and UBact amino acids sequences, and because very few bacteria from the five phyla where UBact is found have been sequenced. [5]

Bacteria from the phyla where UBact is found interact with humans, [12] [13] and are found in the human gut microbiota. [14] In marine systems, the most frequently encountered nitrogen-oxidizing bacteria are related to the UBact encoding Nitrospina gracilis [15] From the knowledge accumulated about the Pup-proteasome system and its importance in bacterial durability and disease causing ability, [16] [17] the homologous UBact-proteasome system is expected to have similar impact on the gram-negative bacteria where it is found. In addition to humans, animals such livestock and fish that eat from the ground or swim in water are expected to be constantly exposed to UBact containing bacteria in the soil and water respectively.

From evolutionary perspective, the finding of the UBact-proteasome system in gram-negative bacteria suggests that either the Pup/UBact-proteasome systems evolved in bacteria prior to the split into gram positive and negative clades over 3000 million years ago [18] or, that these systems were acquired by different bacterial lineages through horizontal gene transfer(s) from a third, yet unknown, organism. In support of the second possibility, two UBact loci were found in the genome of an uncultured anaerobic methanotrophic Archaeon (ANME-1;locus CBH38808.1 and locus CBH39258.1). More possibilities exist.

Update: UBact is also found in the gram-negative bacterial phylum Gemmatimonadota (e.g., A0A2E8WA32, A0A2E3J6F7, A0A2E7JSE3) in the candidate phylum "Latescibacteria" (previously known as WS3; e.g., A0A3D2RHP4, A0A3D5FTR6, A0A3D4H075, and A0A3B8MMW3), in the phylum "Abditibacteriota" (previously candidate phylum FBP; e.g., A0A2S8SU03), and in the phylum Candidatus Bipolaricaulota (e.g., H5SEU7 and H5SQ95).

See also

Related Research Articles

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In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.

Gram-negative bacteria Group of bacteria that do not retain the Gram stain used in bacterial differentiation

Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane.

Proteasome Protein complexes which degrade unnecessary or damaged proteins by proteolysis

Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.

Ubiquitin Regulatory protein

Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.

Actinomycetota Phylum of bacteria

The Actinomycetota are a phylum of mostly Gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to soil systems. In soil they help to decompose the organic matter of dead organisms so the molecules can be taken up anew by plants. While this role is also played by fungi, Actinomycetota are much smaller and likely do not occupy the same ecological niche. In this role the colonies often grow extensive mycelia, like a fungus would, and the name of an important order of the phylum, Actinomycetales, reflects that they were long believed to be fungi. Some soil actinomycetota live symbiotically with the plants whose roots pervade the soil, fixing nitrogen for the plants in exchange for access to some of the plant's saccharides. Other species, such as many members of the genus Mycobacterium, are important pathogens.

The Aquificota phylum is a diverse collection of bacteria that live in harsh environmental settings. The name Aquificota was given to this phylum based on an early genus identified within this group, Aquifex, which is able to produce water by oxidizing hydrogen. They have been found in springs, pools, and oceans. They are autotrophs, and are the primary carbon fixers in their environments. These bacteria are Gram-negative, non-spore-forming rods. They are true bacteria as opposed to the other inhabitants of extreme environments, the Archaea.

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<i>Bacteroidota</i> Phylum of Gram-negative bacteria

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Secretion Controlled release of substances by cells or tissues

Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

Periplasm

The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the periplasmic space in gram-negative bacteria. Using cryo-electron microscopy it has been found that a much smaller periplasmic space is also present in gram-positive bacteria.

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<i>Mycobacterium smegmatis</i> Species of bacterium

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PVC superphylum Superphylum of bacteria

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Proteasomeaccessory factor E is an ATP-independent proteasome activator of Mycobacterium tuberculosis that forms 12-fold symmetric rings and interacts with the 20S proteasome core particle through a conserved carboxyl-terminal motif to activate peptide and protein degradation.

Ubiquitin-like protein Family of small proteins

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References

  1. 1 2 Pearce, M. J.; Mintseris, J.; Ferreyra, J.; Gygi, S. P.; Darwin, K. H. (2008). "Ubiquitin-Like Protein Involved in the Proteasome Pathway of Mycobacterium tuberculosis". Science. 322 (5904): 1104–1107. doi:10.1126/science.1163885. PMC   2698935 . PMID   18832610.
  2. 1 2 Wang T, Darwin KH, Li H (November 2010). "Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation". Nature Structural & Molecular Biology. 17 (11): 1352–7. doi:10.1038/nsmb.1918. PMC   2988878 . PMID   20953180.
  3. ↑ Universal protein resource accession number P9WHN4 for "Prokaryotic ubiquitin-like protein Pup" at UniProt.
  4. ↑ Liao S, Shang Q, Zhang X, Zhang J, Xu C, Tu X (2009). "Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered protein". 422 (2). Biochemical Journal: 207–215. doi:10.1042/BJ20090738. PMID   19580545.{{cite journal}}: Cite journal requires |journal= (help)
  5. 1 2 3 4 5 6 7 8 Lehmann G, Udasin RG, Livneh I, Ciechanover A (February 2017). "Identification of UBact, a ubiquitin-like protein, along with other homologous components of a conjugation system and the proteasome in different gram-negative bacteria". Biochemical and Biophysical Research Communications. 483 (3): 946–950. doi:10.1016/j.bbrc.2017.01.037. PMID   28087277.
  6. ↑ Delley CL, Müller AU, Ziemski M, Weber-Ban E (November 2017). "Prokaryotic Ubiquitin-Like Protein and Its Ligase/Deligase Enyzmes [sic]". Journal of Molecular Biology. 429 (22): 3486–3499. doi:10.1016/j.jmb.2017.04.020. hdl: 20.500.11850/191988 . PMID   28478282.
  7. ↑ Vijay-Kumar S, Bugg CE, Cook WJ (April 1987). "Structure of ubiquitin refined at 1.8 A resolution". Journal of Molecular Biology. 194 (3): 531–44. doi:10.1016/0022-2836(87)90679-6. PMID   3041007.
  8. ↑ Chen X, Solomon WC, Kang Y, Cerda-Maira F, Darwin KH, Walters KJ (September 2009). "Prokaryotic ubiquitin-like protein pup is intrinsically disordered". Journal of Molecular Biology. 392 (1): 208–17. doi:10.1016/j.jmb.2009.07.018. PMC   2734869 . PMID   19607839.
  9. ↑ Liao S, Shang Q, Zhang X, Zhang J, Xu C, Tu X (August 2009). "Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered protein". The Biochemical Journal. 422 (2): 207–15. doi:10.1042/BJ20090738. PMID   19580545.
  10. ↑ "Ubiquitin-like protein Pup [Leptospirillum ferriphilum] - Protein - NCBI".
  11. ↑ "Ubiquitin-like protein UBact [Leptospirillum ferriphilum] - Protein - NCBI".
  12. ↑ Kowarsky M, Camunas-Soler J, Kertesz M, De Vlaminck I, Koh W, Pan W, et al. (September 2017). "Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA". Proceedings of the National Academy of Sciences of the United States of America. 114 (36): 9623–9628. doi: 10.1073/pnas.1707009114 . PMC   5594678 . PMID   28830999.
  13. ↑ Drancourt M, Prebet T, Aghnatios R, Edouard S, Cayrou C, Henry M, et al. (September 2014). "Planctomycetes DNA in febrile aplastic patients with leukemia, rash, diarrhea, and micronodular pneumonia". Journal of Clinical Microbiology. 52 (9): 3453–5. doi:10.1128/JCM.01207-14. PMC   4313204 . PMID   24920769.
  14. ↑ Dubourg G, Lagier JC, Armougom F, Robert C, Audoly G, Papazian L, Raoult D (February 2013). "High-level colonisation of the human gut by Verrucomicrobia following broad-spectrum antibiotic treatment". International Journal of Antimicrobial Agents. 41 (2): 149–55. doi:10.1016/j.ijantimicag.2012.10.012. PMID   23294932.
  15. ↑ Lücker S, Nowka B, Rattei T, Spieck E, Daims H (2013). "The Genome of Nitrospina gracilis Illuminates the Metabolism and Evolution of the Major Marine Nitrite Oxidizer". Frontiers in Microbiology. 4 (27): 27. doi: 10.3389/fmicb.2013.00027 . PMC   3578206 . PMID   23439773.
  16. ↑ Becker SH, Darwin KH (March 2017). "Bacterial Proteasomes: Mechanistic and Functional Insights". Microbiology and Molecular Biology Reviews. 81 (1): e00036–16. doi:10.1128/MMBR.00036-16. PMC   5312241 . PMID   27974513.
  17. ↑ Elharar Y, Roth Z, Hecht N, Rotkopf R, Khalaila I, Gur E (March 2016). "Posttranslational regulation of coordinated enzyme activities in the Pup-proteasome system". Proceedings of the National Academy of Sciences of the United States of America. 113 (12): E1605-14. Bibcode:2016PNAS..113E1605E. doi: 10.1073/pnas.1525185113 . PMC   4812726 . PMID   26951665.
  18. ↑ Marin J, Battistuzzi FU, Brown AC, Hedges SB (February 2017). "The Timetree of Prokaryotes: New Insights into Their Evolution and Speciation". Molecular Biology and Evolution. 34 (2): 437–446. doi: 10.1093/molbev/msw245 . PMID   27965376.
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