The Role of Heparin in the Prion Proteins Aggregation
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The cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored plasma membrane protein, whose pathogenic isoform is a noxious inducer of numerous fatal neurodegenerative diseases. Sulfated glycosaminoglycans (GAGs), including heparin, are associated with prion proteins (PrP) misfolding and aggregation. However, the role of heparin in the PrP aggregation is less clear. Here, we investigate the PrP aggregation process through atomic force microscopy (AFM). Our result demonstrates heparin promotes protein aggregation by facilitating the formation of oligomers during the early nucleation stage. Full-length PrP binding to heparin is a two-step process that includes the formation of 1) short sporadic oligomers and 2) long stable fibrils. In addition, the force spectroscopy shows that interaction between PrP and heparin binding is mainly through electrostatic forces with an estimated Gibbs free energy of 28.53 kcal/mol.