Prion Disease Essay

Prion disease is the best example to show that protein conformational change can even lead toinfectious disease.In the year of 1982, prion term coined by Stanley Prusiner and co-workers from “proteinaceous infectious particle”. Prion protein is found in two different forms: a cellular form of prion protein (PrPc) and scrapie isoform of prion protein (PrPSc). Properly folded form is denoted as PrPc while misfolded form is denoted as PrPSc . The PrPc is an α-helix-rich glycoprotein that is approximately 250 amino acids in length. It is encoded by the prion protein gene (Prpn) which is located on chromosome 20. PrPc is commonly found on neuronal cell membrane by a glycosyl phosphatidylinositol (GPI). However, it is also expressed on other cells such as leukocytes and dendritic cells. PrPc has been assumed a variety of functions including cell adhesion, intracellular signaling, copper metabolism, and protective antioxidant activity. PrPc is highly conserved protein among mammals during evolution. When we examine the primary structure of the protein, PrPc consist of a signal peptide (1-22), five octapeptide repeats (PHGGGWGQ) (51-91), a highly conserved hydrophobic domain (106-126), and a GPI (glycol sylphosphatidylinositol) anchor. Furthermore, PrPc contains two N-linked glycosylation sites (181Asn-Ile-Thr and 197Asn-Phe-Thr). Thus, they get dynamic and flexible properties and the glycan covers prevent intermolecular and intramolecular interactions. His96 and His111 are found in metal binding domains of PrPc and they compose coordination sites with metal ions (Cu+2, Zn+2, Mn+2, Ni+2). A disulfide bond between Cys179 and Cys214 play a significant role for proper folding of PrPc .PrPSc can be defined as an infectious isoform of PrPc and...

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...holesterol and sphingomyelin rich area on cell surface (known as lipid raft). PrPc is bound to lipid membranes through its GPI anchor. While leaving PrPc from the membranes by catalysis of phosphatidylinositol phospholipase C (PIPLC), PrPSc show resistance to PIPLC. When binding of PrPc to the lipid membranes, PrPc is degraded or converted into PrPSc form.The group of prion diseases, including Creutzfeldt-Jakob (CJD), fatal familial insomnia (FFI), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS) are seen in humans, and in similar fashion scrapie, bovine spongiform encephalopathy (mad cow disease), chronic wasting diseases (CWD), transmissible mink encephalopathy (TME), feline spongiform encephalopathy (FSE) diseases are observed in animals. All of these diseases give similar neurological symptoms such as dysmnesia, depression, sense disturbances, and psychosis.