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Structural Insights into Substrate Recognition and Processing by the 20S Proteasome

Faculty of Biology, Technion-Israel Institute of Technology, 32000 Haifa, Israel
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Academic Editor: Paolo Cascio
Biomolecules 2021, 11(2), 148; https://doi.org/10.3390/biom11020148
Received: 3 January 2021 / Revised: 18 January 2021 / Accepted: 21 January 2021 / Published: 24 January 2021
(This article belongs to the Special Issue Regulating Proteasome Activity)
Four decades of proteasome research have yielded extensive information on ubiquitin-dependent proteolysis. The archetype of proteasomes is a 20S barrel-shaped complex that does not rely on ubiquitin as a degradation signal but can degrade substrates with a considerable unstructured stretch. Since roughly half of all proteasomes in most eukaryotic cells are free 20S complexes, ubiquitin-independent protein degradation may coexist with ubiquitin-dependent degradation by the highly regulated 26S proteasome. This article reviews recent advances in our understanding of the biochemical and structural features that underlie the proteolytic mechanism of 20S proteasomes. The two outer α-rings of 20S proteasomes provide a number of potential docking sites for loosely folded polypeptides. The binding of a substrate can induce asymmetric conformational changes, trigger gate opening, and initiate its own degradation through a protease-driven translocation mechanism. Consequently, the substrate translocates through two additional narrow apertures augmented by the β-catalytic active sites. The overall pulling force through the two annuli results in a protease-like unfolding of the substrate and subsequent proteolysis in the catalytic chamber. Although both proteasomes contain identical β-catalytic active sites, the differential translocation mechanisms yield distinct peptide products. Nonoverlapping substrate repertoires and product outcomes rationalize cohabitation of both proteasome complexes in cells. View Full-Text
Keywords: 20S proteasome; protein degradation; intrinsically disordered proteins; enzyme functional cycle; peptides; peptidome; proteome; oxidative stress 20S proteasome; protein degradation; intrinsically disordered proteins; enzyme functional cycle; peptides; peptidome; proteome; oxidative stress
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MDPI and ACS Style

Sahu, I.; Glickman, M.H. Structural Insights into Substrate Recognition and Processing by the 20S Proteasome. Biomolecules 2021, 11, 148. https://doi.org/10.3390/biom11020148

AMA Style

Sahu I, Glickman MH. Structural Insights into Substrate Recognition and Processing by the 20S Proteasome. Biomolecules. 2021; 11(2):148. https://doi.org/10.3390/biom11020148

Chicago/Turabian Style

Sahu, Indrajit, and Michael H. Glickman. 2021. "Structural Insights into Substrate Recognition and Processing by the 20S Proteasome" Biomolecules 11, no. 2: 148. https://doi.org/10.3390/biom11020148

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