Ubiquitin mediated processes

• Avidity - tight binding

  Selectivity - right binding
• Types of autophagy:

  • Chaperone mediated autophagy
  • Microautophagy - involves lysosomes
  • Macroautophagy (refered to as autophagy)
• Chaperone mediated autophagy - soluble cytosolic proteins containing a degenerate sequence motif are degraded by the lysosome, chaperone and LAMP2A dependent
• macroautophagy involves sequestration and transport of protein aggregates and organelles (within membrane limited structures) to the lysosomes for degradation, can be ubiquitin dependent
• Benefits of autophagy:

  • Non essential components can be recycled to provide energy and amino acids for protein synthesis during cell starvation
  • Removal of misfolded protein aggregates, damaged organelles, invading intracellular bacteria eyc
• Autophagy stages

  1. Formation of phagophore / isolation membrane
  2. Phagophore expansion
  3. Cargo recognition
  4. Vesicle completion - autophagosome
  5. Fusion - autolysosome
  6. Degradation and recycling
• Ubiqutination in autophagy:

  1. Protein on surface of substrate is ubiquitinated with K63 linked chains
  2. Adaptor proteins recognise the ubiquitin modified cargos
  3. Cargo incorporated into autophagosome by autophagy receptor
  4. Also binds to lipid anchored LC3-II protein
• Lipid anchored proteins (LC3) are ubiquitin like proteins in tertiary structure
• LC3-II incorporates in to the developing phagophore via its lipid tail
• Autophagy receptors simultaneously bind ubiquitin (UBD) and LC3-II (LIR)