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Proteasomes and protein conjugation across domains of life

Nature Reviews Microbiology volume 10, pages 100–111 (2012)Cite this article

Subjects

Key Points

  • Proteasomes (energy-dependent proteases that are important in protein quality control and cell signalling) are conserved in their basic structure and function among eukaryotes, archaea and actinobacteria.

  • In eukaryotes, proteins targeted for degradation by proteasomes are often covalently modified by the attachment of ubiquitin chains through a process termed ubiquitylation. This involves E1 ubiquitin-activating, E2 ubiquitin-conjugating and E3 ubiquitin ligase enzymes.

  • Mycobacteria (a group of actinobacteria) have a system of protein conjugation termed pupylation, which can target proteins for degradation by proteasomes. During pupylation, a small protein modifier known as prokaryotic ubiquitin-like protein (Pup) is covalently attached to the Lys residues of target proteins by an enzymatic mechanism that is distinct from ubiquitylation.

  • The archaeon Haloferax volcanii generates protein conjugates through a process called sampylation, in which ubiquitin-like protein modifiers (small archaeal modifier protein 1 (Samp1) or Samp2) are attached to substrate proteins. Sampylation requires the presence of the E1 homologue UbaA, revealing a close functional relationship between sampylation and ubiquitylation. Sampylation is predicted to be widespread among the archaea but can function in the absence of E2 and E3 enzyme homologues (at least, according to genome sequences).

  • An ongoing question is whether sampylation targets proteins for proteasome-mediated degradation and/or serves in non-proteolytic control mechanisms. Archaeal proteasomes are known to be important for cell growth and stress survival and can be regulated by post-translational modifications.

Abstract

Like other energy-dependent proteases, proteasomes, which are found across the three domains of life, are self-compartmentalized and important in the early steps of proteolysis. Proteasomes degrade improperly synthesized, damaged or misfolded proteins and hydrolyse regulatory proteins that must be specifically removed or cleaved for cell signalling. In eukaryotes, proteins are typically targeted for proteasome-mediated destruction through polyubiquitylation, although ubiquitin-independent pathways also exist. Interestingly, actinobacteria and archaea also covalently attach small proteins (prokaryotic ubiquitin-like protein (Pup) and small archaeal modifier proteins (Samps), respectively) to certain proteins, and this may serve to target the modified proteins for degradation by proteasomes.

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Figure 1: Basic structures of proteasomes across domains of life.
Figure 2: Ordered reaction cycle in protein degradation by proteasomes.
Figure 3: Ubiquitylation as a signal for degradation.
Figure 4: Pupylation as a signal recognized by proteasomes in bacteria.
Figure 5: Sampylation and proteasomes in archaea.

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Acknowledgements

The author thanks the reviewers for providing important insights and constructive comments, and apologizes for not citing many important references that have contributed to this Review, owing to space limitations. Work in the author's laboratory is funded in part by grants from the US National Institutes of Health (GM57498) and the US Department of Energy Office of Basic Energy Sciences (DE-FG02-05ER15650).

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  1. Department of Microbiology and Cell Science, University of Florida, Gainesville, 32611-0700, Florida, USA

    Julie Maupin-Furlow

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Sampylation and its connection to sulphur transfer. (PDF 269 kb)

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Glossary

Actinobacteria

A group of Gram-positive bacteria with high genomic GC contents, including Mycobacterium, Rhodococcus, Streptomyces and Frankia spp. Actinobateria have been shown to have proteasomes.

HslV and ClpP proteases

Self-compartmentalized proteins that are located within bacteria and eukaryotic organelles, harbour proteolytic active sites and associate with the hexameric rings of AAA+ ATPases to form HslUV, ClpXP and ClpAP proteases, which mediate the energy-dependent degradation of structured proteins.

TROSY NMR

A method for analysing large biomolecules such as proteasomes by measuring the cancellation between dipolar coupling and chemical shift anisotropy or between different dipolar couplings.

E1-like superfamily

A group of conserved proteins that catalyse the adenylation of proteins containing a β-grasp fold, such as ubiquitin. Examples include the E1 enzyme used to activate ubiquitin during ubiquitylation, MoeB (which activates MoaD during sulphur transfer to form molybdenum cofactor (MoCo)) and ThiF (which activates ThiS in sulphur transfer during thiamine biosynthesis).

JAMM–MPN+ enzymes

A family of proteins that typically coordinate a catalytic zinc ion. Members of this family include the yeast protein Rpn11 (or POH1 in humans), an isopeptidase that is required for the deubiquitylase activity of 26S proteasomes.

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Maupin-Furlow, J. Proteasomes and protein conjugation across domains of life. Nat Rev Microbiol 10, 100–111 (2012). https://doi.org/10.1038/nrmicro2696

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