Fibrillization of recombinant bovine prion protein (rec-PrP) in vitro

Abstract

112 Conversion of normal prion protein ( PrP c ) from the conformation with predominantly α -helical structure into the conformation rich in β -structures ( PrP sc , β -PrP, and PrP res ) underlies the pathogenesis of prion diseases, a special class of degenerative diseases of the nervous system of humans and animals. Prion diseases, or transmissible spongiform encephalopathies (TSEs) of humans, include the Creutzfeldt–Jakob disease (CJD), the Gerstmann–Straussler–Scheinker syndrome, new variant of CJD, kuru, as well as the fatal familial insomnia. The most well-known transmissible spongiform encephalopathies of animals are scrapie of sheep, chronic wasting disease of deer and moose, and bovine spongiform encephalopathy (mad cow disease) [1]. In the course of development of transmissible spongiform encephalopathies, amyloid fibrils (the so-called scrapie-associated fibrils) are formed in brain tissue of both animals and humans. These fibrils consist of β -PrP and are partially resistant to proteolysis. Transmissible spongiform encephalopathies differ in clinical symptoms, neuropathology, neuroanatomical distribution of PrP sc in tissues, and incubation period. It is believed that this heterogeneity of transmissible spongiform encephalopathies is determined by distinctions in the trimeric structure of pathological isoforms of PrP sc [1]. To understand the molecular mechanisms of conversion, the causes of strain differences of causative agents of transmissible spongiform encephalopathies, and interspecies transmission of prion diseases, transformation of recombinant PrP (rec-PrP) of human and different animal species into amyloid fibrils has been performed in vitro in the past years in several laboratories [3–6]. It was shown that the amino acid sequence of PrP markedly affects the formation and morphology of fibrils.