Protein Denaturation and Misfolding

Proteins can be denatured, that is, unfolded & disorganized, making them non-functional.
Extreme changes in the temperature or ph breaks the bond that maintain protein structure so that the functional activity of proteins is lost. This is called denaturation.

Common denaturant agents are: Heat, organic solvents, strong acids or bases, detergents, ions of heavy metals such as lead & mercury.
  • High temperature
  • Extremes of pH
  • High concentration of compounds such as urea or guanidine hydrochloride
  • Solutions of detergents such as sodium dodecyl sulphate(SDS)
   Proteins Misfolding is most commonly caused by a gene mutation, which produces an altered protein. e.g. Amyloid protein that spontaneously aggregates in many degenerative disease (Alzheimer’s disease).

The prion protein (PrP) is an infectious protein that converts non infectious (PrP) into infectious form, which precipitates. PrP is implicated as the causative agent of the transmissible spongioform encephalopathies, including Creutzfeld-Jacob Disease.

Accessory proteins, including protein disulphide isomerases, peptidyl cis-trans isomerases, and molecular chaperones assist proteins to fold correctly in the cell.


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