Topic 21: Protein Turnover and Amino Acid Catabolism

Question 1

Describe the ubiquitin pathway

Answer 1

Ubiquitin is activated and attached to proteins using a group of three enzymes
E1: Ubiquitin activating enzyme
E2: Ubiquitin-conjugating enzyme
E3: Ubiquitin-protein ligase

In most cases, ubiquitin tagged target proteins are subjected to degradation, in which the protein complexes are recognized by the 26S proteasome, a large multienzyme complex to mediate protein degradation. This whole process called ubiquitination which includes following three critical steps:

Firstly, ubiquitin needs to be activated from its precursor by adding to E1 through an ATP-dependent manner, and activated ubiquitin is then transferred to the ubiquitin-conjugating enzyme E2

Secondly, E2 interacts with E3 to identify the substrate, and by which ubiquitin is attached to the target protein

Thirdly, the ubiquitin conjugated protein is recognized by the 26S proteasome, and through which, the target protein is degraded to small peptides or amino acids by the proteasome enzymes. Of note, ubiquitin can be released by the deubiquitinating enzymes (DUBs), and therefore, ubiquitin conjugation to target substrates is a reversible process