Figure 1. Trypsin significantly digests PrP^C while preserving almost full-length PrP^Sc.

A. Schematic of the full-length mature PrP sequence, PK-digested PrP^Sc and PrP^C, and trypsin-digested PrP^Sc and PrP^C. Trypsin cleavage sites are indicated by triangles, with gray triangles lying within the PK-resistant core and red triangles indicating expected cleavage sites. B. 50 µg/ml trypsin or PK was incubated with normal (ctrl), vCJD MM (codon 129 polymorphism), sCJD MM, and sCJD MV BHs. Samples were separated by SDS-PAGE and immunoblotted with POM2, 3F4, and POM17 antibodies. An actin immunoblot was performed as a proteolysis control. C. Trypsin removes the octarepeats and 3F4 epitope of PrP^C, but not helix one. Normal and vCJD BHs were digested with 0, 25, 50, 75 or 100 µg/ml trypsin and then analyzed by immunoblotting with POM2, 3F4, and POM1 antibodies.