17.Protein transport in cell organelles. Post-translational modifications of proteins. Aging and degradation of proteins.

Question 1

Post-translational modifications of proteins

Answer 1

Post- translational modifications are chemical changes, i.e. involve breaking and forming covalent bonds.
They include:
-partial proteolysis
-glycosylation
-phosphorylation
-fatty acid addition
-acetylation
-ubiquitination

Partial Proteolysis:

-Proteases: Remove specific polypeptide segments.
-Signal Peptides: Excised after protein delivery.
-Folding Assistance: Segments cut after proper folding (e.g., insulin C-peptide).
-Activation: Inactive precursors activated by proteolysis (e.g., digestive enzymes, clotting factors, caspases).

Phosphorylation/Dephosphorylation:

Phosphorylation: Addition of phosphate from ATP to serine, threonine, or tyrosine by kinases.
Reversibility: Phosphatases remove phosphate groups.
Activity Regulation: Proteins exist in active/inactive phosphorylated states.
Importance: Essential for cell cycle control.

Question 2

Aging and degradation of proteins

Answer 2

Protein aging results in conformational changes that cannot be repaired and the protein must be destroyed. This is done through:

Proteasome-Mediated Degradation:

-Proteasomes: ATP-dependent complexes degrading tagged proteins.
-Targets: Misfolded/denatured proteins, short-lived regulatory proteins (e.g., mitotic cyclins, transcription factors, tumor suppressors).
-Tagging: Proteins are tagged with a polyubiquitin chain (at least four ubiquitins) signaling degradation.

Process:
-Structure: Proteasomes are hollow, barrel-shaped cylinders with proteases.
-Degradation: Polyubiquitinated proteins enter the proteasome and are broken down into polypeptides and amino acids.
-Recycling: Ubiquitin molecules are released and recycled by deubiquitinating enzymes (DUBs).

Pathological Conditions:
-Decreased Degradation: Caused by mutations in ubiquitin-activating enzymes, leading to protein accumulation (e.g., Angelman syndrome, Alzheimer’s disease).
-Increased Degradation: Overexpression of degradation proteins, leading to accelerated protein degradation (e.g., HPV infections).