The only component of the infectious scrapie prion identified to date is a protein designated PrPSc. A posttranslational process converts the cellular PrP isoform (PrPC) into PrPSc. Denatured PrPSc was digested with endoproteases, and the resulting fragments were isolated by HPLC. By both mass spectrometry and Edman sequencing, the primary structure of PrPSc was found to be the same as that deduced from the PrP gene sequence, arguing that neither RNA editing nor protein splicing feature in the synthesis of PrPSc. Mass spectrometry also was used to search for posttranslational chemical modifications other than the glycosylinositol phospholipid anchor attached to the C-terminus and two Asn-linked oligosaccharides already known to occur on both PrPSc and PrPC. These results contend that PrPSc molecules do not differ from PrPC at the level of an amino acid substitution or a posttranslational chemical modification; however, we cannot eliminate the possibility that a small fraction of PrPSc is modified by an as yet unidentified posttranslational process or that PrPC carries a modification that is removed in the formation of PrPSc. It seems likely that PrPSc differs from PrPC in its secondary and tertiary structure, but the possibility of a tightly bound, disease-specific molecule which purifies with PrPSc must also be considered.

Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing

There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled?

A 'unified theory' of prion propagation.

Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da

A method for sterilizing products to inactivate biological contaminants such as viruses, bacteria, yeasts, molds, mycoplasmas and parasites is disclosed. The method involves irradiating the product at a low dose rate from about 0.1 kGy/hr. to about 3.0 kGy/hr. for a period of time sufficient to sterilize the product. The method does not destroy sensitive materials such as blood and blood components. Further, the method does not require pre-treatment of the product such as freezing, filtration or the addition of chemical sensitizers.

Method for sterilizing products

Scrapie is a fatal, central nervous system disease of sheep and goats caused by a serially transmissible agent (Cuille and Chelle 1936) that passes bacterial filters (Cuille and Chelle 1938; Wilson et al. 1950). Serial transmissions at high dilutions of inoculum demonstrate that the agent is self-propagating. Filterability establishes that it is subcellular. Other estimates of size (see below) based on sedimentation velocity, filtration, exclusion chromatography and sensitivity to ionizing radiation place the scrapie agent with the smaller viruses.

The scrapie agent: "a virus by any other name".

Estimation of scrapie nucleic acid MW from standard curves for virus sensitivity to ionizing radiation

Robert G. Rohwer

Papers

Estimation of scrapie nucleic acid MW from standard curves for virus sensitivity to ionizing radiation.

Alzheimer's disease transmission: possible artifact due to intercurrent illness.