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Cited by 28Ubiquitin and proteasome pathwaysEnzyme Structure and FunctionParasitic Infections and Diagnostics

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Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores

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Jespersen, Nathan, Ehrenbolger, Kai, Winiger, Rahel R., Svedberg, Dennis, Vossbrinck, Charles R., Barandun, Jonas·2022·Nature Communications
DOI 10.1038/s41467-022-34691-xPMC PMC9666519

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Abstract

Proteasomes play an essential role in the life cycle of intracellular pathogens with extracellular stages by ensuring proteostasis in environments with limited resources. In microsporidia, divergent parasites with extraordinarily streamlined genomes, the proteasome complexity and structure are unknown, which limits our understanding of how these unique pathogens adapt and compact essential eukaryotic complexes. We present cryo-electron microscopy structures of the microsporidian 20S and 26S proteasome isolated from dormant or germinated Vairimorpha necatrix spores. The discovery of PI31-like peptides, known to inhibit proteasome activity, bound simultaneously to all six active sites within the central cavity of the dormant spore proteasome, suggests reduced activity in the environmental stage. In contrast, the absence of the PI31-like peptides and the existence of 26S particles post-germination in the presence of ATP indicates that proteasomes are reactivated in nutrient-rich conditions. Structural and phylogenetic analyses reveal that microsporidian proteasomes have undergone extensive reductive evolution, lost at least two regulatory proteins, and compacted nearly every subunit. The highly derived structure of the microsporidian proteasome, and the minimized version of PI31 presented here, reinforce the feasibility of the development of specific inhibitors and provide insight into the unique evolution and biology of these medically and economically important pathogens.

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Metadata

Authors
Jespersen, N., Ehrenbolger, K., Winiger, R. R., Svedberg, D., Vossbrinck, C. R., & Barandun, J.
Affiliations
  • Science for Life Laboratory (SE)
  • Connecticut Agricultural Experiment Station (US)
Corresponding author
Barandun, Jonas
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-11-15
Volume
13
Issue
1
Pages
6962-6962
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-34691-x
PMC
PMC9666519
OpenAlex
W4309332483
Cited by
28
References
4
Citations by year
2026: 7 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 1
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Kempe Foundation (JCK-1918)
  • Vetenskapsrådet (05973, 2018-, 2019-02011, 201805973)
  • Umeå Universitet (2018-05973)
  • Kempestiftelserna (JCK-1918, 2018-05973)
  • Stockholms Universitet
  • Science for Life Laboratory
  • H2020 European Research Council (948655)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
Keywords
microsporidia, proteasome, Vairimorpha necatrix, proteasome inhibitors, dormant spores, spore germination, 20S proteasome, 26S proteasome, proteasome structure, proteostasis, intracellular pathogens
MeSH terms
Peptides, Phylogeny, Spores, Microsporidia, Cryoelectron Microscopy, Proteasome Endopeptidase Complex

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