8ADN

Vairimorpha necatrix 20S proteasome from spores

8ADN の概要

• エントリーDOI: 10.2210/pdb8adn/pdb
• EMDBエントリー: 15365
• 分子名称: Proteasome Inhibitor 31-Like, Proteasome subunit beta type-3, Proteasome subunit beta type-4, ... (15 entities in total)
• 機能のキーワード: peptidase activity, reductive evolution, bound peptide, microsporidia, hydrolase
• 由来する生物種: Vairimorpha necatrix; 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 757794.99

構造登録者

Jespersen, N.,Ehrenbolger, K.,Winiger, R.,Svedberg, D.,Vossbrinck, C.R.,Barandun, J. (登録日: 2022-07-08, 公開日: 2022-11-23, 最終更新日: 2024-10-16)

主引用文献

Jespersen, N.,Ehrenbolger, K.,Winiger, R.R.,Svedberg, D.,Vossbrinck, C.R.,Barandun, J.
Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores.
Nat Commun, 13:6962-6962, 2022

PubMed 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.

PubMed: 36379934
DOI: 10.1038/s41467-022-34691-x

実験手法

ELECTRON MICROSCOPY (2.77 Å)