Ubiquitination of Proteins and Protein Degradation

Summary

This video explains the process of ubiquitination, where a ubiquitin protein is covalently linked to a lysine residue of target proteins. The purpose of ubiquitination is to tag proteins for degradation, especially misfolded or unnecessary proteins, by marking them for destruction by proteasomes. The video describes the role of enzymes E1, E2, and E3 in the ubiquitination process, and explains how the tagged proteins are degraded by proteasomes into peptides. Additionally, it mentions prions, which resist degradation by proteasomes. Viewers are encouraged to like and subscribe for more content.

Takeaways

• 🔗 Ubiquitination is the process where ubiquitin proteins are covalently linked to lysine residues of target proteins.
• 🔬 Ubiquitination marks proteins for destruction or degradation, particularly misfolded, toxic, or unnecessary proteins.
• ⚙️ Ubiquitination is also involved in some signaling pathways, helping switch them on or off by degrading proteins.
• ⚡ The ubiquitination process is initiated by three types of enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase enzyme).
• 💡 E1 enzyme activates ubiquitin by forming a thioester bond between ubiquitin and itself, in an ATP-dependent process.
• 🔄 E2 enzyme transfers the activated ubiquitin from the E1 enzyme to its own cysteine residue.
• 🎯 E3 enzyme facilitates the transfer of ubiquitin from E2 to the lysine residue of the target protein, forming an isopeptide bond.
• 📏 Proteins can be mono-, multi-, or poly-ubiquitinated depending on the number of ubiquitin molecules attached.
• 🏭 The degradation of ubiquitinated proteins is carried out by proteasomes, particularly the 26S proteasome, which consists of 20S proteasome and 19S caps.
• 🧩 Proteasomes break down the tagged proteins into short peptides, recycling ubiquitin in the process.

Q & A

What is ubiquitination?

Ubiquitination is a biochemical process in which a ubiquitin protein is covalently linked to the lysine residue of target proteins. This process often tags proteins for degradation.

What type of bond is formed between ubiquitin and the lysine residue of the target protein?

An isopeptide bond is formed between the lysine residue of the target protein and ubiquitin.

What is the purpose of ubiquitination?

The purpose of ubiquitination is to tag proteins for destruction or degradation, particularly proteins that are misfolded, toxic, or no longer needed by the cell. It can also play a role in regulating signaling pathways by degrading specific proteins.

What enzymes are involved in the ubiquitination process?

The enzymes involved in ubiquitination include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligase enzymes (E3).

What role does the E1 enzyme play in ubiquitination?

The E1 enzyme, also known as ubiquitin-activating enzyme, links itself with the carboxyl end of ubiquitin through a thioester bond. This step is energy-dependent and requires ATP.

How does the E2 enzyme contribute to ubiquitination?

The E2 enzyme, or ubiquitin-conjugating enzyme, transfers the activated ubiquitin from the E1 enzyme to its cysteine residue, preparing it for the next step in the process.

What is the function of the E3 enzyme in ubiquitination?

The E3 enzyme, or ubiquitin ligase, facilitates the transfer of ubiquitin from the E2 enzyme to the lysine residue of the target protein, forming an isopeptide bond between them.

What are the different types of ubiquitination?

Proteins can undergo mono-ubiquitination (single ubiquitin attachment), multi-ubiquitination (multiple ubiquitin molecules attached at different sites), or poly-ubiquitination (a chain of ubiquitins attached to a single lysine residue).

What is the structure of the proteasome, and how does it function in protein degradation?

The proteasome consists of two alpha rings and two beta rings, forming the 20S core particle. This core particle is capped by a 19S regulatory particle, forming the 26S proteasome. The proteasome recognizes ubiquitinated proteins, degrades them into peptides, and recycles the ubiquitin molecules.

What happens to prions during the degradation process?

Prions, which are misfolded proteins, are resistant to degradation by proteasomes. This makes them difficult to degrade, leading to the persistence of prion-related diseases.