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The Disordered Landscape of the 20S Proteasome Substrates and the Mechanism of Their in vitro and in vivo Degradation.
Author(s) -
Shaul Yosef,
Myres Nadav,
Biran Assaf,
Reuven Nina
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.795.14
Subject(s) - intrinsically disordered proteins , proteasome , chemistry , proteostasis , in vitro , microbiology and biotechnology , rna splicing , proteome , biophysics , rna , biochemistry , computational biology , biology , gene
Proteasomal degradation is the main route of regulated proteostasis. The 20S proteasome is the core particle (CP) responsible for the catalytic activity of all proteasome complexes. Intrinsically disordered proteins (IDPs) being naturally unfolded may enter the catalytic core of the 20S proteasome. However, what are the attributes of the IDPs that are 20S CP substrates remained an open question. Based on a proteomic analysis of the degradome of the 20S CP activity in vitro we identified a subset of IDPs that are preferential 20S CP substrates (20S‐IDPs). The 20S‐IDPs are highly disordered, having significantly more protein binding partners and subjected to intensive post‐translational modification. Interestingly, the majority of the 20S‐IDPs are RNA binding proteins including mainly those involved in splicing and mRNA processing. Cellular peptidome analysis revealed a group of proteins with the 20S‐IDP attributes, suggesting that 20S is active in the cells. To further substantiate this notion we identified sequence motifs that are preferred 20S‐IDPs cleavage sites and found that IDPs with this motif are highly labile in the cells. We further found 50 amino acid region of the one of the 20S subunits that specifically recognizes IDP and termed it IDP Trapper. The Trapper in isolation binds IDPs and blocks their degradation both in vitro and in the cells. We propose a model whereby a group of IDPs is selectively targeted to the 20S CP in facilitating IDP degradation possibly by the mechanism of 20S gate opening.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .