NR ACBD
AU Buschmann,A.; Kuczius,T.; Bodemer,W.; Groschup,M.H.
TI Cellular prion proteins of mammalian species display an intrinsic partial proteinase K resistance
QU Biochemical and Biophysical Research Communications 1998 Dec 30; 253(3): 693-702
PT journal article
AB Prion diseases are characterized by the intraneuronal accumulation of a pathological isoform (PrPsc) of host-encoded prion protein (PrPc). While PrPsc displays a partial resistance, PrPc is easily degraded by this enzyme. As it turned out in our experiments, PrPc of six species is initially degraded to an intermediate fragment of 25-28 kDa prior to complete proteolysis which was solely detected by antibodies binding to epitopes carboxy-terminally of amino acid 144 of PrPc. The intermediate fragment thus lacked the aminoterminus of PrPc. These findings are well in line with the putative structure of PrPc: the amino-terminus consists of a highly flexible and thus more proteinase K sensitive tail while the carboxy-terminus is folded into possibly more resistant alpha-helices and beta-sheets. We observed significant differences in the PK sensitivities of PrPc from six different species and from three ovine PrP alleles, while no remarkable variation was seen in PrPc from six regions of an ovine brain. This indicates that variations in the sequence of PrP may alter its three-dimensional structure and consequently change its sensitivity towards proteolytic enzymes.
MH Animal; *Brain Chemistry; Cattle; Comparative Study; Drug Resistance; Endopeptidase K/*pharmacology; Hamsters; Human; Mammals/genetics/*metabolism; Mice; Mink; PrPc Proteins/genetics/*metabolism; PrPsc Proteins/metabolism; Sheep/genetics; Species Specificity; Support, Non-U.S. Gov't; Tissue Distribution
AD Anne Buschmann, Martin H. Groschup, Federal Research Centre for Virus Diseases of Animals, Institute of Immunology, Tübingen, Germany
SP englisch
PO USA