Conserved homologues of the Hrd1 ubiquitin ligase target for degradation proteins that persistently or aberrantly engage the endoplasmic reticulum translocon, including mammalian apolipoprotein B (apoB; the major protein component of PVC Shade Mesh low-density lipoproteins) and the artificial yeast protein Deg1-Sec62.A complete understanding of the molecular mechanism by which translocon-associated proteins are recognized and degraded may inform the development of therapeutic strategies for cholesterol-related pathologies.Both apoB and Deg1-Sec62 are extensively post-translationally modified.
Mass spectrometry of a variant of Deg1-Sec62 revealed that the protein is acetylated at the N-terminal methionine and two internal lysine residues.N-terminal and internal acetylation regulates the degradation of a variety of unstable proteins.However, preventing N-terminal and internal acetylation had no detectable consequence for Hrd1-mediated proteolysis of Deg1-Sec62.
Our data highlight the importance of empirically validating the role of post-translational modifications and sequence motifs on protein degradation, even when such elements Nail Repair have previously been demonstrated sufficient to destine other proteins for destruction.