PA28αβ reduces size and increases hydrophilicity of 20S immunoproteasome peptide products

Mary Raule, Fulvia Cerruti, Nadia Benaroudj, Rebekka Migotti, Julia Kikuchi, Angela Bachi, Ami Navon, Gunnar Dittmar, Paolo Cascio*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

The specific roles that immunoproteasome variants play in MHC class I antigen presentation are unknown at present. To investigate the biochemical properties of different immunoproteasome forms and unveil the molecular mechanisms of PA28 activity, we performed in vitro degradation of full-length proteins by 20S, 26S, and PA28αβ-20S immunoproteasomes and analyzed the spectrum of peptides released. Notably, PA28αβ-20S immunoproteasomes hydrolyze proteins at the same low rates as 20S alone, which is in line with PA28, neither stimulating nor preventing entry of unfolded polypeptides into the core particle. Most importantly, binding of PA28αβ to 20S greatly reduces the size of proteasomal products and favors the release of specific, more hydrophilic, longer peptides. Hence, PA28αβ may either allosterically modify proteasome active sites or act as a selective "smart" sieve that controls the efflux of products from the 20S proteolytic chamber.

Original languageEnglish
Pages (from-to)470-480
Number of pages11
JournalChemistry and Biology
Volume21
Issue number4
DOIs
Publication statusPublished - 24 Apr 2014
Externally publishedYes

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