Updated: 3/8/2020

Protein Folding and Degradation

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
4
0
0
Topic
Folding
  • Overview
    • required for a protein to achieve a proper tertiary protein structure
    • involves heat shock proteins (Hsp)
      • essential for normal protein folding
      • some function as chaperones and some function as chaperonins
    • the more mutated a protein, the more help it needs from chaperones
    • if a protein is not folding properly, a chaperone may send it directly for degradation
    • clinical relevance
      • cystic fibrosis
        • pathogenesis
          • 3 nucleotide deletion on chromosome 7
          • ΔF508 mutation in chloride channel (CFTR) ↓ stability of the protein and ↑ folding time 
          • instead of insertion into the plasma membrane the protein is degraded in the Golgi apparatus
          • ↓ chloride conductance results in ↓ Na+ and Cl reabsorption in sweat glands
        • presentation
          • ↓ water content of mucus which results in a thick mucus that cannot be cleared
            • respiratory infections
            • nasal polyps
            • malabsorption
            • meconium ileus
            • biliary cirrhosis
  • Chaperones
    • types
      • Hsp70
        • associates with directly with the ribosome
        • hides hydrophobic regions of protein to allow for proper folding
        • ATP hydrolysis required
        • essential
      • Hsp90
        • used for fewer proteins than Hsp70
        • ATP hydrolysis required
        • essential
        • role in folding mutant proteins in cancer
  • Chaperonins
    • group 1
      • Hsp60
        • ring shaped
        • ATP hydrolysis required
        • called GroEL/GroES in prokaryotes
        • peptide chain enters the cage and it is capped
        • once folded the cap is removed and the protein is released
    • group 2
      • TRiC/CCT
        • composed of 8 Hsp60s
        • similar function to GroEL/GroES
        • required for folding of actin and tubulin
Degradation
  • Ubiquitination
    • cell's mechanism to mark a protein for destruction
    • mechanism 
      • several copies of ubiquitin added to a misfolded/unneeded protein
      • polyubiquitinated protein enters the proteasome
      • protein hydrolyzed into peptide fragments
  • Defects in destruction of misfolded proteins
    • inability to send degraded proteins to proteasome results in accumulation in ER
    • examples
      • α1-antitrypsin (AAT) deficiency 
        • normally synthesized by hepatocytes and exocytosed into circulation
          • inhibit proteases
        • in AAT deficiency misfolded α1-antitrypsin accumulates in ER and damages hepatocytes 
          • PAS+ granules
        • many genetic variations
          • MC are Z and S variants due to point mutations
          • co-dominant allelic expression
        • presentation
          • micronodular cirrhosis
          • fibrosis
        • test with PCR

Please rate topic.

Average 4.8 of 8 Ratings

Questions (4)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Evidence (1)
EXPERT COMMENTS (8)
Private Note