NR AWIK
AU Kuczius,T.; Grassi,J.; Groschup,M.H.
TI Amino terminal truncation of prion proteins in human, sheep, cattle, and mouse
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-21
PT Konferenz-Poster
AB Prion diseases are fatal neurodegenerative disorders which affect both humans and animals. The pathogenic mechanism is associated with the conversion of normal prion protein (PrPc) to a pathological isoform (PrPsc) followed by conformational change. The C-terminal domain of PrPc (amino acids (aa) 125-231) is composed of three alpha-helices and two ß-sheets and has two glycosylation sites. The amino (N-) terminal region (aa 23-124) containing the octapeptide region is unstructured with a flexible polypeptide chain. In physiological metabolism the N-terminal region can be forfeited by cleavage. Thus, it is supposed that cleavage may provide a mechanism for downregulation of PrPc activities. Truncated forms of 18 kDa were found by antibodies recognizing carboxyl (C-) terminal sequences after deglycosylation of the protein samples. In our study, however, we identified fragments of approximately 18 kDa even after immunoprecipitation without deglycosylation. We examined the forming of the C-terminal fragment and compared the expressions in human, cattle, sheep and mouse. Proteins of brain homogenates were immunoprecipitated and signals of PrPc were quantified by densitometry. Interestingly, noticeable formation of the truncated forms differed among species. High levels of the C-terminal fragment were found in mouse brains and low amounts in sheep brains. Fragments of PrPc in cattle were >3 kDa higher compared with sheep PrPc. Moreover, cattle PrPc were detected as a double band differing in the molecular mass of approximately of 2 kDa. Our data indicate that the C-terminal fragment is a major product of physiological PrPc metabolism in different species, generated by cleavage and detectable by immunoprecipitation.
AD T. Kuczius: Institute for Hygiene, University Hospital Muenster, Robert Koch-Str. 41, 48149 Münster, Germany; J. Grassi: CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, 91191 Gif sur Yvette, France; M.H. Groschup: Institute for Novel and Emerging Infectious Diseases, Friedrich Loeffler-Institute, Boddenblick 5a, 17493 Greifswald - Isle of Riems, Germany. E-mail: tkuczius@uni-muenster.de
SP englisch
PO Italien