The C-terminus of the PSMA3 proteasome subunit preferentially traps intrinsically disordered proteins for degradation

ABSTRACT: Degradation of intrinsically disordered proteins (IDPs) by a non-26S proteasome process does not require proteasomal targeting by polyubiquitin. However, whether and how IDPs are recognized by the non-26S proteasome, including the 20S complex, remains unknown. Analyses of protein interactome datasets revealed that the 20S proteasome subunit, PSMA3, preferentially interacts with many IDPs. Employing in vivo and cell-free experiments, it was found that a 69-amino-acids-long fragment at the C-terminus of PSMA3 is sufficient to bind the disordered protein p21. A recombinant PSMA3 C-terminus 69 fragment is sufficient to interact with many IDPs, and is therefore designated an IDP trapper. A recombinant IDP trapper blocks the degradation of many IDPs in vitro by the 20S proteasome, possibly by competing with the native trapper. In addition, over a third of the PSMA3 trapper-binding proteins have previously been identified as 20S proteasome substrates, and based on published datasets many of the trapper binding proteins are associated with the intracellular proteasomes. The PSMA3-trapped IDPs that are proteasome substrates have the unique features previously recognized as characteristic 20S proteasome substrates in vitro. We propose a model whereby the PSMA3 C-terminal region traps a subset of IDPs to facilitate their proteasomal degradation.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Kidney

SUBMITTER: Yishai Levin  

LAB HEAD: Yosef Shaul

PROVIDER: PXD024791 | Pride | 2023-03-11

REPOSITORIES: Pride