Sialylation of Prion Protein Controls the Rate of Prion Amplification, the Cross-Species Barrier, the Ratio of PrPSc Glycoform and Prion Infectivity
Figure 7
Schematic diagrams illustrating that prion polymerization and PrPSc glycoform ratio are controlled by sialic acid residues of glycans.
A, B. Sialylation of glycans impedes prion amplification in PMCAb due to electrostatic repulsion between sialic acid residues on the PrPSc surface. Desialylation of a substrate facilitates prion polymerization in dsPMCAb. Due to strain-specific differences in PrPSc structures, PrPC desialylation speeds up polymerization of strains of synthetic origin (B) much stronger than strains of natural origin (A). C. Electrostatic repulsion between sialic acid residues limits percentage of diglycosylated glycoforms that can be accommodated in PrPSc. Desialylation of PrPC in dsPMCAb changes the ratio of glycoforms in PrPSc in favor of diglycosylated glycoforms. PrPC monomers are depicted as blue circles; glycosyls are shown as yellow circles where presence of terminal sialic acid residues is shown as a red glow. Electrostatic repulsion is represented with lightning bolts.