Certain proteins may need to be modified after being translated in order to assume a final functional state

• These post-translational modifications involve a variety of covalent changes to the protein, including:

  • The formation of disulphide bridges between cysteine residues
    

  • Conjugation with other proteins or inorganic cofactors (e.g. the haeme group in haemoglobin)
    

  • Chemical modifications (such as glycosylation or phosphorylation) to improve structural stability or moderate biological activity
    

  • The removal of amino acids from the polypeptide chain (proteolytic cleavage) to mediate protein folding 
    

An example of a protein that requires modification before it can function is human insulin

• Insulin is synthesised as an inactive precursor molecule called pre-proinsulin and undergoes a two-step modification process

  • Preproinsulin is converted into proinsulin when a signal sequence is removed in the rough endoplasmic reticulum (the signal sequence directed the ribosome to translate the protein directly into the rough ER)
    

  • As the proinsulin folds within the Golgi complex, opposite ends of the protein (the A and B chains) are linked by disulphide bridges – the intervening segment (called the C peptide) is removed
    

  • The resulting mature insulin is then packaged into secretory vesicles and stored until use (regulatory secretion)