Protein Design

Protein Folding and Dynamics - The Student's Guide

[Excerpt] Not all proteins when synthesized fold to their native state in a spontaneous and independent process. Several types of molecular chaperone are involved in the transport, folding and assembly of newly synthesized proteins. However, sometimes this system fails and some protein misfolds. These proteins can simply be destroyed by proteolytic enzymes, but in some cases the misfolded protein can start to form aggregates. Prion diseases (also known as Transmissible Spongiform Encephalopathies, which include CJD, BSE, and Scrapie) are a thus far unique example of how these aggregates can be pathogenic. In these diseases, the formation of misfolded prion protein (PrPSc) promotes the formation of more misfolded protein, because PrPSc binds to the normal form (PrPC), and converts it to PrPSc. This leads to the formation of large plaques in the brain which are associated with the death of neurons. Autopsies of victims show that their brain tissue is littered with small holes - hence "Spongiform". It is interesting to note that PrPC has an in vivo half-life of about 6 hours whereas PrPSc shows no signs of degradation, suggesting it has gained resistance to the normal mechanisms the cell uses to dispose of misfolded proteins.

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