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9.9: 프로테아솜
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Molecular Biology

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The Proteasome
 

9.9: The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.

In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase). The synergy of all these three enzymes helps to attach ubiquitin molecules to the target proteins covalently.

The proteasome, a large multi-subunit protease, can hence differentiate between a healthy protein and target protein by recognizing the ubiquitin chain on the target protein. Once the proteasome recognizes the ubiquitin chain, it unfolds the target protein and ultimately degrades it. The leftover peptides of the substrate protein are then released into the cytosol for further processing.

Targeted destruction of proteins is critical to the well-being of the cell, and any alterations in the ubiquitin-proteasome pathway can lead to disease. For example, if misfolded proteins are not degraded, they form protein aggregates in the cytoplasm. Such protein aggregates can lead to prominent neurodegenerative disorders such as Parkinson, Huntington, and Alzheimer's.

On the contrary, excess quality control by the ubiquitin-proteasome pathway may also lead to disease. For example, the destruction of misfolded but partially functional chloride ion-channels leads to cystic fibrosis, a life-threatening disorder in humans.


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Proteasome Protein Degradation Ubiquitin-proteasome Pathway Ubiquitin Ligase Degradation Signals Polyubiquitinated Proteins ATP-dependent Protease Complex Core Caps Proteolytic Active Sites Deubiquitinase ATP Hydrolysis Unfolded Protein Proteases

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