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Mechanism of Boc3Arg Mediated Degradation
Author(s) -
Shi Yuntao,
Long Marcus,
Kobjack Aimee,
Li Shican,
Hedstrom Lizbeth
Publication year - 2015
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.29.1_supplement.883.9
Subject(s) - proteasome , degradation (telecommunications) , protein degradation , chemistry , ubiquitin , microbiology and biotechnology , ligand (biochemistry) , mechanism (biology) , biochemistry , biology , receptor , computer science , gene , telecommunications , philosophy , epistemology
The degradation of target proteins can be induced by a recognition ligand linked to tert‐butyl carbamate‐protected arginine (Boc3Arg) in a process that involves the proteasome. This research explores the mechanism of such Boc3Arg induced degradation and the role of the Boc3Arg tag. Boc3Arg induced degradation does not appear to involve ubiquitination of the target protein, nor does the Boc3Arg tag appear to perturb the structure of the target protein. Various Boc3Arg analogs stimulate the activity of purified 20S proteasome against peptide substrates by up to 4‐fold. A Boc3Arg‐linked ligand promotes the degradation of eDHFR by the pure 20S proteasome. A simple model for Boc3Arg mediated degradation is proposed: the Boc3Arg tag localizes target proteins to the 20S proteasome, while at the same time stimulating 20S proteasome activity.