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26S Proteasome and Ubiquitin

Kathy Duong, Kaitlyn Greenwood, Aliyah Jackson, Van Hopkins, Allison Weber
Protein/Organellar Function Assignment
BIOL324: Collins
March 8, 2020
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Introduction-Van:​ Cells require protein management to remain healthy and functional.

Proteasomes allow cells to degrade faulty proteins to prevent disease and ensure protein
equilibrium. The process of degradation occurs once the proteins are marked by ubiquitination.
Once ubiquitin is added to the protein, the proteasomes can remove the protein and prevent cell
complications that cause diseases. Proteasomes are found in all eukaryotic cells and some
bacteria​1​. Proteasomes are essential for cell processes and help prevent disease when functioning
properly.
Proteasome Structure and Location-Allison and Van​: Structurally, the 26S proteasome is
made of two sub-complexes, a catalytic core particle (20S CP) and one or two terminal
regulatory particles (19S RP)​2,3​. There are four axially stacked rings in a barrel-shaped structure
within the proteasome​5​. The 20S CP is the portion that degrades proteins, and is capped at each
end by regulatory proteins​2​. These are known as 19S RP and they bind to the ends of a 20S CP.
The 19S RP recognizes, unfolds, activates, and translates proteins into the 20S CP​3​. The 26S
proteasome can be found in the nucleus and cytoplasm of all eukaryotic cells.
Proteasome Activity-Allison and Aliyah:​ ​Proteasome activity changes depending on what the
cell needs. Apoptosis, proliferation, and environmental factors (oxidative stress, disease states,
etc.) can all alter the activity of the proteasome. When proteins are folded incorrectly,
proteasomes must remove them from the cell to maintain homeostasis and regulate protein
​ . In eukaryotes, protein degradation is usually carried out with the
signaling pathways 4,5​
ubiquitin-proteasome system (UPS)​6​.
Proteasome Function-Aliyah: ​The proteasome is a protein complex responsible for proteolysis.
Polymerization of ubiquitin, a signaling molecule, serves as a degradation signal for target
proteins; the destruction of a protein is initiated by covalent attachment of a chain consisting of
several copies of ubiquitin, through the concerted actions of a network of proteins, including the
E1-3 enzymes that activate, conjugate and ligate ubiquitin. The polymerized chain acts as a
signal that shuttles the target proteins to the proteasome, where the substrate is proteolytically
broken down​5​.
Deficiency of Proteasome-Kathy:​ ​A deficiency in proteasomes would induce unnecessary
apoptosis instead of eliminating the non-functional proteins​5​.​ ​Besides protein degradation, it is a
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crucial organelle that provides antigen peptides so T-cells can recognize these antigens for
immunity responses​5​. Proteasomes are also involved in replenishing amino acids through the
breakdown of proteins. Without the presence of proteasomes, cells have to waste numerous
amounts of energy synthesizing amino acids.
Protein Structure-Kaitlyn: ​A majority of the ubiquitin protein is involved in hydrogen
bonding, making up the secondary structure. Its unique secondary structure consists of a beta
bulge and symmetrical hydrogen bonding including three turns and a half turn alpha helices. The
carboxyl terminal interacts with UBE3A to become activated and mark proteins​3​.
Protein Location-Kaitlyn: ​Ubiquitin is found throughout cells. The majority is in the cytoplasm
where it acts as a protein marker​7​. It has been found to function in the nucleus as a quality
control manager of DNA replication and translation​4,7​. Ubiquitin has interactions at the cell
membrane, marking channels and proteins for degradation​7​.
Protein Function-Kathy: ​ Ubiquitination by ubiquitin regulates proteasomes. Ubiquitin binds to
the target protein which signals the proteasome for proteolysis. Ubiquitination starts with
ubiquitin-activating enzyme (E1) activating ubiquitin with ATP, which is followed by the
transferring of ubiquitin to the ubiquitin-conjugating enzyme (E2) that then transfers the
ubiquitin to ubiquitin protein ligase (E3)​7​. E3 attaches ubiquitin to the target protein that signals
for degradation. The linkage is an isopeptide bond on the C terminus of ubiquitin to the ε-amino
group of a lysyl on the target protein​7​. This pathway involves many enzymes and steps, for
regulatory purposes.
Summary:​ Cells must have efficient processes for proper homeostasis. Proteasomes create a
stable protein balance, and require ubiquitin for regulation.The proteasome is a large protein
complex responsible for degradation of intracellular proteins. A decrease in proteasome activity
results in unnecessary apoptosis, unavailability to antigens peptides and amino acids. Ubiquitin
exists throughout cells in various forms, allowing it to perform a range of functions.
Ubiquitination is a result from three enzymes that activate, transfer, and attach ubiquitin to the
target protein for destruction.
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Works Cited
1. Marshall, Richard S., and Richard D. Vierstra. “Dynamic Regulation of the 26S Proteasome: From Synthesis to
Degradation.” ​Frontiers in Molecular Biosciences​, vol. 6, 2019, doi:10.3389/fmolb.2019.00040.

2. Livneh, I., Cohen-Kaplan, V., Cohen-Rosenzweig, C. ​et al.​ The life cycle of the 26S proteasome: from birth,
through regulation and function, and onto its death. ​Cell Res​ 26, 869–885 (2016). ​https://doi.org/10.1038/cr.2016.86​.

3. Tanaka, Keiji. “The proteasome: overview of structure and functions.” ​Proceedings of the Japan Academy. Series
B, Physical and biological sciences​ vol. 85,1 (2009): 12-36. doi:10.2183/pjab.85.1.

4. Mikecz, A. Von. “The Nuclear Ubiquitin-Proteasome System.” ​Journal of Cell Science,​ vol. 119, no. 10, 2006,
pp. 1977–1984., doi:10.1242/jcs.03008.

5. Lecker, Stewart H, et al. “Protein Degradation by Ubiquitin-Proteasome Pathway in Normal and Disease States.”
American Society of Nephrology​, 13 Apr. 2006, pp. 1807–1819., doi: 10.1681/ASN.2006010083.

6. Gan, Jin et al. “Highlighting the Proteasome: Using Fluorescence to Visualize Proteasome Activity and
Distribution.” ​Frontiers in molecular biosciences​ vol. 6 14. 22 Mar. 2019, doi:10.3389/fmolb.2019.00014.

7. Vijay-Kumar S, Bugg CE, Cook WJ. Structure of ubiquitin refined at 1.8 A resolution. ​J Mol Biol​.
1987;194(3):531–544. doi:10.1016/0022-2836(87)90679-6.