ntracellular proteins are targeted for proteolytic degradation in proteasomes uponconjugation with

Intracellular proteins are targeted for proteolytic degradation in proteasomes upon conjugation with ubiquitin. This process is known as ubiquitination and it is a key mechanism for protein catabolism within cells.

Here are the steps of this process:

1. Activation: The first step in ubiquitination is the activation of ubiquitin by an enzyme known as ubiquitin-activating enzyme (E1). This is an ATP-dependent process that results in the formation of a high-energy thioester bond between the carboxyl group of the C-terminal glycine residue of ubiquitin and a cysteine residue in the E1 enzyme.

2. Conjugation: The activated ubiquitin is then transferred to a ubiquitin-conjugating enzyme (E2). This is also a thioester linkage.

3. Ligation: Finally, a ubiquitin ligase enzyme (E3) transfers the ubiquitin from the E2 enzyme to the target protein. The ubiquitin is covalently attached to the protein via an isopeptide bond between the C-terminal glycine of ubiquitin and a lysine residue on the target protein.

4. Polyubiquitination: This process can be repeated multiple times, leading to the formation of a polyubiquitin chain on the target protein. This serves as a signal for degradation by the 26S proteasome.

5. Degradation: The 26S proteasome recognizes and binds to the polyubiquitinated protein, unfolds it and degrades it into small peptides.

This process is crucial for maintaining protein homeostasis within the cell and plays a role in many cellular processes, including cell cycle progression, DNA repair, transcriptional regulation, and response to stress.