| PROTEIN FOLDING AND FOLDING DISEASE
|
| For proteins to function properly, they must fold into the correct shape. Proteins have evolved so that one fold is more favourable than all others, the native state. Numerous proteins assist other proteins in the folding process. These proteins, termed chaperones, include 'heat shock' proteins, hsp 60 and hsp 70, and protein disulfide isomerase. A protein folding disease is a disease that is associated with abnormal conformation of a protein. This occurs in chronic, age-related diseases, such as Alzheimer disease, amyotrophic lateral sclerosis, and Parkinson's disease.
|
| CREUTZFELDT-JACOB DISEASE |
| A 56-year-old male cattle rancher presented with epileptic cramp and dementia and was diagnosed as having Creutzfeldt-Jacob disease, a human prion disease. The prion diseases, also known as transmissible spongiform encephalopathies, are neurodegenerative diseases that affect both humans and animals. This disease in sheep and goats is designated as scrapie, and in cows as spongiform encephalopathy (mad cow disease). The diseases are characterized by the accumulation of an abnormal isoform of a host-encoded protein, prion protein-cellular form (PrPC), in affected brains. |
| Comment. Prions appear to be composed only of PrPSc (Scrapie form) molecules, which are abnormal conformers of the normal, host-encoded protein. PrPC has a high α-helical content and is devoid of β-pleated sheets, whereas PrPSc has a high β-pleated sheet content. The conversion of PrPC into PrPSc involves a profound conformational change. The progression of infectious prion diseases appears to involve an interaction between PrPC and PrPSc, which induces a conformational change of the α-helix-rich PrPC to the β-pleated sheet-rich conformer of PrPSc. PrPSc-derived prion disease may be genetic or infectious. The amino acid sequences of different mammalian PrPCs are similar, and the conformation of the protein is virtually the same in all mammalian species. The central protein of the transmissible agent, or prion, was discovered by Stanley B Prusiner, the Nobel Prize winner in physiology in 1997. |
|
