Figure 6
From: Prion protein self-peptides modulate prion interactions and conversion
Adapted schematic representation of one incubation/sonication cycle of PMCA. Pre-incubated PMCA (A): peptide is allowed to form a bond with PrPC (1), resulting in all PrPC binding peptide (pre-incubation with an excess of peptide). The conversion reaction is initiated by adding PrPSc to the 'sensitized' PrPC (2). It is likely that the peptide is incorporated in formed PrPres during conversion (3). Sonication (4) shears PrPres, but does not release peptide from 'sensitized' PrPC and probably not from the elongated PrPSc (#). The PrPres fragments (some with peptide incorporated) are in turn capable of recruiting and converting 'sensitized' PrPC (5) during the next incubation cycle. Supplemented PMCA (B): the conversion reaction is first initiated by combining PrPC and PrPSc (1). Peptide is immediately added (2), which can bind to either PrPC or PrPSc separately, but is probably only effective when binding both. PrPC is converted, possibly releasing the peptide in the process (3). Sonication (4) shears PrPres, probably releasing the peptide if it is still bound after step 3. The PrPres fragments (unlikely with peptide incorporated, #) are in turn capable of recruiting and converting PrPC (5) during the next incubation cycle. Even though PrPC, PrPres and peptide are all present after sonication, it is likely that fist the PrPC-PrPSc complex is formed (1) before interaction with peptide (2) occurs. However, if the peptide is capable of 'sensitizing' PrPC, the reaction proceeds as described for the pre-incubated PMCA reaction (6). After addition of all ingredients in the first cycle the pre-incubated -and supplemented PMCA reactions will have both unbound and bound peptide available for the following sonication-incubation cycles.