NR AFNI
AU Hope,J.; Multhaup,G.; Reekie,L.J.; Kimberlin,R.H.; Beyreuther,K.
TI Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie
QU European Journal of Biochemistry 1988 Mar 1; 172(2): 271-7
PT journal article
AB Scrapie-associated fibrils (SAF) are disease-specific structures found in extracts of the brains of animals affected with scrapie. These structures are pathological aggregates of a normal host protein (PrP). Abnormal post-translational modification of PrP has been suggested to explain its aberrant properties in scrapie-affected brains and although there is a form of PrP in SAF indistinguishable in size from the protein in uninfected brain, lower-molecular-mass variants of PrP are also found in SAF fractions. We report the characterisation of the multiple forms of PrP found in SAF fractions purified from mouse brain affected by the ME7 strain of scrapie. The quantitatively major forms of PrP in SAF prepared without the use of proteinase K have the amino-terminal sequence Lys-Lys-Arg-Pro-Lys-Pro-Gly-Gly-, identical to that predicted for the amino-terminus of normal mouse brain PrP. However N-terminal cleavage of some PrP does occur in vivo within a domain of repetitive sequences at sites similar to but distinct from those cut by proteinase K in vitro. This suggests the conformation of the protein in aggregates in vivo does not differ extensively from that in detergent-treated SAF in vitro. We conclude that the size diversity of PrP in SAF is only partly due to N-terminal proteolysis and is independent of the proteolysis that occurs if proteinase K is used in the purification of SAF. Apart from proteolytic changes in the structure of PrP, we found a novel, as yet unidentified, amino-acid derivative of the arginine residue at position 3 in mouse PrP, which may predispose PrP to form SAF.
IN Einem Teil der Prionproteine in schonend isolierten scrapie-assoziierten Fibrillen fehlen die ersten etwa 22 Aminosäuren. Diese Abspaltung scheint aber bereits in vivo zu erfolgen, da die Schnittstelle beim Proteinase-K-Verdau in Detergenz nicht die gleiche ist. Außerdem fanden die Autoren eine Variante des Maus-Prionproteins, die offenbar zu verkürzten Inkubationszeiten führt.
MH Amino Acid Sequence; Animal; Arginine/analysis; *Brain Chemistry; Comparative Study; Endopeptidase K; Hamsters; Mice; Molecular Sequence Data; Nerve Tissue Proteins/*analysis; PrP 27-30 Protein; Prions/analysis; Protein Conformation; Scrapie/*metabolism; Serine Endopeptidases/pharmacology; Support, Non-U.S. Gov't
AD Agriculture and Food Research Council, Edinburgh.
SP englisch
PO Westdeutschland