3.10:_The_Proteasome

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<p class="lt-bio-3975" style="background-color: unset;">Protein <strong>degradation</strong> is as essential to the cell as protein <strong>synthesis</strong>. For example, to supply amino acids for fresh protein synthesis, to remove excess enzymes, and to remove transcription factors that are no longer needed. There are two major intracellular devices in which damaged or unneeded proteins are broken down. They are <strong>lysosomes</strong> and <strong>proteasomes</strong></p>

<span id="Lysosomes"></span><span id="Lysosomes"></span><h2 style="background-color: unset;" class="lt-bio-3975">Lysosomes</h2>

<p class="lt-bio-3975" style="background-color: unset;">Lysosomes deal primarily with <strong>extracellular</strong> proteins, e.g., plasma proteins, that are taken into the cell, e.g., by endocytosis. They are cell-surface membrane proteins that are used in receptor-mediated endocytosis. The proteins (and other macromolecules) are engulfed by <strong>autophagosomes.</strong></p>

<figure><img height="285" style="max-width: 748px;" width="380" class="internal" alt="Diagram of a lysosome showing a membrane and labeled Membrane. Inside, various colored circles and squares are labeled Proteins/Enzymes." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/4823/Lysosome.jpg?revision=1" />
<figcaption>Figure 3.10.1: Structure of Lysosome. of lumoreno (via Wikipedia)</figcaption>
</figure>

<span id="Proteasomes"></span><span id="Proteasomes"></span><h2 style="background-color: unset;" class="lt-bio-3975">Proteasomes</h2>

<p class="lt-bio-3975" style="background-color: unset;">Proteasomes deal primarily with endogenous proteins; that is, proteins that were synthesized within the cell such as transcription factors, <strong>cyclins</strong> (which must be destroyed to prepare for the next step in the cell cycle) and proteins encoded by viruses and other intracellular pathogens. Proteasomes also address proteins that are folded incorrectly because of translation errors, or they are encoded by faulty genes or they have been damaged by other molecules in the cytosol. Structure of the Proteasome in the Core Particle (CP) and the Regulatory Particle (RP) as shown in Figure 3.10.2.</p>

<figure><img class="internal" alt="Diagram of miRNA regulation: miRNA binds to mRNA, forming a double helix with a nongreen strip labeled miRNA in a green cell. Arrows indicate binding, with the process labeled Regulation." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/5927/proteasome.png?revision=1" />
<figcaption>Figure 3.10.2: Simplified scheme of the proteosome complex.</figcaption>
</figure>

<p class="lt-bio-3975" style="background-color: unset;">The core particle is made of 2 copies of each of 14 different proteins that are assembled in groups of 7 forming a ring. The 4 rings are stacked on each other (like 4 doughnuts) along a common center (Figure 3.10.3).</p>

<figure><img height="211" width="513" class="internal" alt="Abstract image with dense, intricate patterns. Two red clusters flank a central blue section, creating a symmetrical arrangement. The texture resembles tangled threads or fibers." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/5956/Proteaosome_1fnt_side.png?revision=1" /> <img height="219" width="182" class="internal" alt="Circular molecular structure with alternating red and blue helical patterns densely arranged, creating a complex, symmetrical design on a white background." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/5957/Proteaosome_1fnt_top.png?revision=1" />
<figcaption>Figure 3.10.3: (left) Cartoon representation of a proteasome. Its active sites are sheltered inside the tube (blue). The caps (red; in this case, 11S regulatory particles) on the ends regulate entry into the destruction chamber, where the protein is degraded. (right) view through the poor. Images used with permission from Wikipedia (CC-SA-BY.3.0; Thomas Splettstoesser).</figcaption>
</figure>

<p class="lt-bio-3975" style="background-color: unset;">There are two identical RPs, one at each end of the core particle. Each is made of 19 different proteins (none of them the same as those in the CP). 6 of these are <strong>ATPases</strong> and some of the subunits have sites that recognize the protein <strong>ubiquitin.</strong> Ubiquitin is a small protein (76 amino acids) that is conserved throughout all the kingdoms of life (Figure 3.10.4) and is virtually identical in sequence whether in bacteria, yeast, or mammals. Ubiquitin is used by all these creatures to target proteins for destruction (hence the name based off of the &quot;ubiquitous&quot; term).</p>

<figure><img height="220" width="373" class="internal" alt="A protein structure diagram with blue helices and green sheets. The image shows the N-terminus, C-terminus, and lysine positions 46 and 63, connected by yellow coils." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/5955/Ubiquitin_cartoon-2-.png?revision=2" />
<figcaption>Figure 3.10.4: Cartoon representation of ubiquitin protein, highlighting the secondary structure. from Wikipedia (CC-SA-BY-3.0; Rogerdodd).</figcaption>
</figure>

<span id="The_Process"></span><span id="The_Process"></span><h2 style="background-color: unset;" class="lt-bio-3975">The Process</h2>

<p class="lt-bio-3975" style="background-color: unset;">Proteins destined for destruction are conjugated to a molecule of ubiquitin which binds to the terminal amino group of a lysine residue. Additional molecules of ubiquitin bind to the first forming a chain and this complex then binds to ubiquitin-recognizing site(s) on the <strong>regulatory particle.</strong> The protein is unfolded by the ATPases using the energy of ATP, which is translocated into the central cavity of the core particle. Several active sites on the inner surface of the two middle &quot;doughnuts&quot; break various specific peptide bonds of the chain, which produces a set of peptides averaging about 8 amino acids long. These leave the core particle by an unknown route where they may be further broken down into individual amino acids by peptidases in the cytosol. However, in mammals, they may be incorporated in a class I histocompatibility molecule to be presented to the immune system as a potential <strong>antigen. </strong>The regulatory particle releases the ubiquitins for reuse</p>

<span id="Antigen_Processing_by_Proteasomes"></span><span id="Antigen_Processing_by_Proteasomes"></span><h2 style="background-color: unset;" class="lt-bio-3975">Antigen Processing by Proteasomes</h2>

<p class="lt-bio-3975" style="background-color: unset;">In <strong>mammals</strong>, activation of the immune system leads to the release of the cytokine <strong>interferon-gamma</strong>. This causes three of the subunits in the core particle to be replaced by substitute subunits; the peptides generated in this altered proteasome are picked up by TAP (= <strong>t</strong>ransporter <strong>a</strong>ssociated with antigen <strong>p</strong>rocessing) proteins and transported from the cytosol into the endoplasmic reticulum where each enters the groove at the surface of a class I histocompatibility molecule. This complex then moves through the Golgi apparatus and is inserted in the plasma membrane where it can be &quot;recognized&quot; by CD8<sup><font size="2">+</font></sup> <strong>T cells</strong>. It is probably no coincidence that the genes encoding the three substitute <strong>core particle</strong> subunits, <strong>TAP and all the MHC (major histocompatibility complex)</strong><strong> molecules </strong>are clustered together on the same chromosome (#6 in humans).</p>

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<hr class="autoattribution-divider" /><div class="autoattribution"><p>This page titled <a target="_blank" class="internal mt-self-link" href="/Sandboxes/johnnyphung/biology/03:_The_Cellular_Basis_of_Life/3.10:_The_Proteasome">3.10: The Proteasome</a> is shared under a <a rel="nofollow" href="https://creativecommons.org/licenses/by/3.0" target="_blank">CC BY  3.0</a>  license and was authored, remixed, and/or curated by <a rel="nofollow" target="_blank" href="http://www.biology-pages.info/">John W. Kimball</a> via <a rel="nofollow" href="https://www.biology-pages.info/" target="_blank">source content</a> that was edited to the style and standards of the LibreTexts platform.</p></div>

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