Question

5. (a) What type of post-translational modification direct protein for proteasome degradation? (0.3 pt)

(b) Which amino acid residue on the protein does the modification occur? What is the functional group that modify the protein? What types of bonds link the protein and modification group together? (0.6 pt)

(c) Describe the three functions of the 19S subunit of proteasome (0.6 pt).

(d) Describe the function of the 20S subunit of proteasome (0.2 pt).

Answer 1

5 (a). Ubiquitination is another major post-translational modification that has a major role in protein degradation. Small ubiquitin-related modifiers are responsible for SUMOylation. Since PTM occurs at low levels, it is difficult to characterize them using other established proteomics methods.

b. Attachment of lipid molecules, known as lipidation, often targets a protein or part of a protein attached to the cell membrane.
...Common PTMs by residue.

Each amino acid is attached to another amino acid by a covalent bond, known as a peptide bond. When two amino acids are covalently attached by a peptide bond, the carboxyl group of one amino acid and the amino group of the incoming amino acid combine and release a molecule of water.

c. The 19S particle in eukaryotes consists of 19 individual proteins and is divisible into two subassemblies, a 9-subunit base that binds directly to the α ring of the 20S core particle, and a 10-subunit lid. Six of the nine base proteins are ATPase subunits from the AAA Family, and an evolutionary homolog of these ATPases exists in archaea, called PAN (Proteasome-Activating Nucleotidase).[26] The association of the 19S and 20S particles requires the binding of ATP to the 19S ATPase subunits, and ATP hydrolysis is required for the assembled complex to degrade folded and ubiquitinated proteins. Note that only the step of substrate unfolding requires energy from ATP hydrolysis, while ATP-binding alone can support all the other steps required for protein degradation (e.g., complex assembly, gate opening, translocation, and proteolysis).[27][28] In fact, ATP binding to the ATPases by itself supports the rapid degradation of unfolded proteins. However, while ATP hydrolysis is required for unfolding only, it is not yet clear whether this energy may be used in the coupling of some of these steps.

d. The proteasome functions as an endoprotease. The mechanism of proteolysis by the β subunits of the 20S core particle is through a threonine-dependent nucleophilic attack. ... Such activity requires the proteasome to cleave the substrate protein internally, rather than processively degrading it from one terminus.