Submitted to: Inform
Publication Type: Review Article
Publication Acceptance Date: 11/1/2005
Publication Date: 2/1/2006
Citation: Silva, C.J. 2006. Prions: pathological proteins at the interface of oil and water. Inform. 17(2), pp. 76-77+79.
Technical Abstract: A prion is an infectious isoform (PrPSc) of a normal cellular protein (PrPC). PrPC is a globular protein composed of approximately 209 amino acids, depending on species. It has three post-translational modifications (PTM): a disulfide linkage, two large sugar antennae, and a glycosyl phosphatidylinositol (GPI) anchor to covalently link PrPC to the lipids in the cell membrane. It has three a-helical regions, which comprise 42% of the sequence and two small b-sheet regions comprising 3% of the sequence. Its natural function remains unclear. For a given host, PrPSc and PrPC have the same primary amino acid sequence, disulfide linkage, and post-translational modifications. PrPSc, however, has the capacity to induce PrPC to adopt the PrPSc conformation and thereby propagate an infection that leads to cell death. The secondary structure of PrPSc consists of 43% b-sheet and 30 % a-helix. If PrPSc is completely denatured and then allowed to refold, the resulting protein is PrPC and not PrPSc. This review includes an historical review of the science behind the development of the prion model. It highlights current research on the chemistry and detection of prions. In addition, the crucial role of the GPI anchor in the pathology of this molecule will be discussed.