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• Proteins


  Perform nearly every function carried out on a cellular level
• General protein functions

  • Enzymes
  • Messengers
  • Structural proteins
  • Transporters
  • Receptors
  • Motor proteins
  • Storage proteins
• Why we are interested in proteins

  • Fundamental understanding of biology
  • Use as biotherapeutics – antibodies
  • Use as glycoconjugate vaccines
  • Understanding the molecular basis of disease, especially proteopathies
  • Designing molecules to affect function – drugs
  • As industrial tools
• Proteins can be soluble or membrane-bound
• Understanding the relationship between protein structure and function is required

  
• Protein synthesis


  1. Template-driven

  2. Genetic code provides instructions for order of amino acids

  3. Synthetic machinery reads genetic code

  
• Modular architectures


  Allow diversity through combinatorial nature
• Antibodies


  • Proteins that recognise unique foreign targets
  • On surface of immune system cells
  • Each antibody can bind to a unique nonhuman molecule
• Antibody synthesis


  1. Heavy chain constructed from 3 genetic modules selected from pools

  2. Light chain constructed from 2 genetic modules selected from pools

  3. Imprecise joining of modules amplifies diversity

  4. Modules subject to point mutations, further increasing diversity

  
• The central dogma is intact - direct relationship between gene and protein

  
• Transcriptome


  Complete collection of all RNA found in a cell

  
• RNA splicing


  • Removes stretches of RNA before it is ready to serve as mRNA
  • Depends on environmental conditions
  • Allows a single human gene to code for more than one protein

  
• Proteases are enzymes that cleave proteins and peptides hydrolytically
• Roles of proteases

  • Digestion
  • Tissue remodelling
  • Protein degradation in cellular regulation
  • Thrombosis or blood clotting

  
• Human genome codes for >500 proteases
• Proteolytic processing


  1. N-terminus modification in prokaryotes

  2. Removal of N-terminal methionine

  3. Prokaryotic proteins destined for translocation synthesized as preproteins

  4. Protein targeting in eukaryotes

  5. Insulin is doubly processed
• The central dogma does not fully prescribe the final functional form of proteins
• Wider world of proteins

  • Potential for considerable diversity
  • Final forms of proteins deviate from DNA template
  • No direct relationship between DNA and proteins as suggested by central dogma
  • Elaboration and modification allows for even more diversity and complexity

  
• Post-translational modifications (PTMs) contribute to protein diversity and complexity