Prion disease is the best example to show that protein conformation change can even lead to infectious disease. In 1982, the term prion was coined by Stanley Prusiner and his colleagues as an “infectious protein particle”. The prion protein comes in two different forms: a cellular form of prion protein (PrPc) and a scrapie prion protein isoform (PrPSc). A correctly folded shape is denoted by PrPc, while an incorrectly folded shape is denoted by PrPSc. PrPc is an α-helix-rich glycoprotein approximately 250 amino acids long. It is encoded by the prion protein gene (Prpn) located on chromosome 20. PrPc is commonly found on the membrane of neuronal cells by a glycosyl phosphatidylinositol (GPI). However, it is also expressed on other cells such as leukocytes and dendritic cells. PrPc performs a variety of functions, including cell adhesion, intracellular signaling, copper metabolism, and protective antioxidant activity. PrPc is a highly conserved protein in mammals during evolution. When we look at the primary structure of the protein, PrPc consists of a signal peptide (1-22), five octapeptide repeats (PHGGGWGQ) (51-91), a highly conserved hydrophobic domain (106- 126) and a GPI (glycol sylphosphatidylinositol). Additionally, PrPc contains two N-linked glycosylation sites (181Asn-Ile-Thr and 197Asn-Phe-Thr). Thus, they acquire dynamic and flexible properties and the glycan covers prevent intermolecular and intramolecular interactions. His96 and His111 are found in the metal-binding domains of PrPc and compose coordination sites with metal ions (Cu+2, Zn+2, Mn+2, Ni+2). A disulfide bond between Cys179 and Cys214 plays an important role in the correct folding of PrPc. PrPSc can be defined as an infectious isoform of PrPc and...... middle of paper ...... cholesterol- and sphingomyelin-rich area on the cell surface (called lipid raft). PrPc is bound to lipid membranes via its GPI anchor. By leaving PrPc from membranes by catalysis of phosphatidylinositol phospholipase C (PIPLC), PrPSc exhibits resistance to PIPLC. Upon binding of PrPc to lipid membranes, PrPc is degraded or converted to the PrPSc form. The group of prion diseases, including Creutzfeldt-Jakob (CJD), fatal familial insomnia (FFI), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS) are observed in humans, and similarly , scrapie, bovine spongiform encephalopathy (mad cow disease), chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and feline spongiform encephalopathy (FSE) are observed in animals . All of these diseases cause similar neurological symptoms such as dysmnesia, depression, sensory disturbances and psychosis..