NR AEHI
AU Gabizon,R.; McKinley,M.P.; Prusiner,S.B.
TI Purified prion proteins and scrapie infectivity copartition into liposomes
QU Proceedings of the National Academy of Sciences of the United States of America 1987 Jun; 84(12): 4017-21
PT journal article
AB Considerable evidence indicates that the scrapie prion protein (PrP 27-30) is required for infectivity. Aggregates of PrP 27-30 form insoluble amyloid rods that resist dissociation by nondenaturing detergents. Mixtures of the detergent cholate and phospholipids were found to solubilize purified PrP 27-30 in the form of detergent-lipid-protein complexes. Removal of the cholate by dialysis resulted in the formation of closed liposomes. Both the detergent-lipid-protein complexes and the liposomes often but not always exhibited a 10-fold increase in scrapie infectivity compared to that observed with the rods. No evidence for a prion-associated nucleic acid could be found when the phospholipid vesicles containing PrP 27-30 were digested with nucleases and Zn2+ under conditions that allowed hydrolysis of exogenously added nucleic acids. No filamentous or rod-shaped particles were found amongst prion liposomes by electron microscopy in our search for a putative filamentous "scrapie virus." The partitioning of PrP 27-30 and scrapie infectivity into phospholipid vesicles contends that PrP 27-30 has a central role in scrapie pathogenesis, establishes that the prion amyloid rods are not essential for infectivity, and argues that prions are fundamentally different from viruses.
IN Aus scrapieinfizierten Hirnen isolierte und proteolytisch an den Enden angeknabberte Prionproteinfragmente PrP 27-30 bilden in vitro wasserunlösliche, amyloide Proteinstangen. Gemische aus Phospholipiden und dem Detergens Cholsäure bilden mit gereinigtem PrP 27-30 Protein-Lipid-Detergens-Komplexe und bringen so das PrP 27-30 in Lösung. Entfernt man durch Dialyse die Cholsäure, dann bilden sich geschlossene Liposomen ohne filamentöse oder stäbchenförmige Elemente. Oft, aber nicht immer erwiesen sich die Protein-Lipid-Detergens-Komplexe und Liposomen als verglichen mit den amyloiden Proteinstäbchen 10-fach infektiöser. Dabei ist aber unklar, ob diese Zunahme der Infektiosität auf eine Zunahme aktiver Enden, eine gesteigerte Verfügbarkeit einer gleichbleibenden Infektiosität, oder auf einen anderen Effekt zurückzuführen ist.
MH Animal; DNA/metabolism; Hamsters; Light; *Liposomes; Microscopy, Electron; Nucleic Acid Hybridization; Prions/*analysis/pathogenicity/ultrastructure; Scattering, Radiation; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Viral Proteins/genetics/*isolation & purification
SP englisch
PO USA
ZF kritische Zusammenfassung von Roland Heynkes