Post-Translational Modification of Proteins

Genes can produce multiple proteins using RNA splicing, addition, foliding, modifications and targeting e.g. K+ channels in squid giant axon 1 gene = 4.5 x1015 distinct channel types

To become a functional protein:

• Unique 3D folding
• Modifications e.g. cofactor binding, uses kinases or peptidases
• Sorted into correct location
• Assembly correctly with other protein subunits

Required information for processes is within primary amino acid sequence

EX - Glutamic acid to y-carboxy-glutamate (COO- group) by vitamin k-dependent enzyme system

• e.g. prothrombin (blood clotting) - first 10 glutamates carboxylated so it can bind to calcium moore effciently = bind to cell membrane to coagulate

EX (stable modifications) - conversion of lysine to 5-hydroxylysine in collagen by lysyl hydroxylase

Other examples inc. glycosylation, phosphorylation (reversible)

2 enzymes promote correct folding by catalysing modification reactions:

• Peptidyl prolyl isomerase - catalyses proline isomerisation (interconversion of prolines cis cyclic structure to trans)
• Protein disulphide isomerase (PDI) - promotes correct disulphide bond formation (nearest -SH groups bonding is not always desirable)

Signal sequences direct proteins to correct cellular address. N-terminal peptides - range between 15-60 amino acids and are cleaved by peptidases once transport is complete:

• Signal peptide - direct to ER
• Transit peptide - direct to mitochondira/chloroplasts

Sometimes 2 signal sequences to be more specific e.g. chloroplast then thylakoid lume

Anchor protiens to membranes by attaching fatty acids/lipids:

• Mytistolylation - protein with glycine at end terminus = adds C14 fatty acid
• Palmitoylation - protein with internal cysteine = C16 fatty acid
• Pronylation - protein with cysteine 4 residues on C-terminus = add prenyl lipid
• GPI anchor helps binding to lumerial or extracellular surfaces of membrane

Anchor protiens to membranes by attaching fatty acids/lipids:

• Mytistolylation - protein with glycine at end terminus = adds C14 fatty acid
• Palmitoylation - protein with internal cysteine = C16 fatty acid
• Pronylation - protein with cysteine 4 residues on C-terminus = add prenyl lipid
• GPI anchor helps binding to lumerial or extracellular surfaces of membrane

• EX - Insulin Biosynthesis

• EX - zymogens are enzyme precursors that are activated in a proteolytic cascade 
  • e.g. trypsinogen -> trypsin in duodenum (reduces damage to other cells)

Helps to stabalise the protein - allows enzymes to work:

• Fe-S centres (electron transport)
• Coordination of metals
• Binding of tetrapyrroles e.g. haem, chlorophyll

Often needed to function:

• Oligomer of identical subunits
• Oligomer of two different subunits e.g. ribosomes
• Large complex of many different subunits

Regulate protein activity. Not modified constants - dynamic molecules.

• Glycosylation
• Oxidation
• Mehtylation
• Acetylation
• Phosphorylation
• Ubiquitnation
• Carbonylation