Abstract
Three carbamylated derivatives of reduced mouse prion protein (mPrP) were isolated during the aborted oxidative folding in the presence of urea. These three prion protein derivatives (mPrP-a, mPrP-b, and mPrP-c) exist as monomer in the acidic solution (pH < 2.0) and exhibit prevalent random coil structure. However, they undergo rapid aggregation and transformation to a predominant β-sheet structure upon exposure to ionic buffer with pH greater than 3.0. The stability of aggregates of mPrP conformers is in part dependent upon the time that they were allowed to develop. The nascent aggregates comprise a significant fraction of loosely packed mPrP monomers that can be dissociated by treatment with strong acidic solution. Matured aggregates acquired through prolonged sample incubation contain more tightly packed mPrP monomers that cannot be dissociated by strong acid but can be disaggregated by denaturant. The properties of reversible aggregation of mPrP-a, mPrP-b, and mPrP-c bear a striking resemblance to that observed with aggregates of hamster PrPSC.
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Lu, BY., Atanasov, I., Zhou, Z.H. et al. Reversible Aggregation of Mouse Prion Protein Derivatives with PrPSC-Like Structural Properties. J Protein Chem 22, 115–126 (2003). https://doi.org/10.1023/A:1023466728762
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DOI: https://doi.org/10.1023/A:1023466728762