Reversible monomer-oligomer transition in human prion protein

The structure and the dissociation reaction of oligomers PrPoligo from reduced human prion huPrP(C)(23-231) have been studied by H-1-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The H-1-NMR and fluorescence spectral feature of the oligomer is consistent with the notion that the N-terminal residues including all seven Trp residues, are free and mobile, while residues 105 similar to 210, comprising the AGAAAAGA motif and S1-Loop-HelixA-Loop-S2-Loop-HelixC, are engaged in intra- and/or inter-molecular interactions. By increasing pressure to 200 MPa, the oligomers tend to dissociate into monomers which may be identified with PrPC*, a rare metastable form of PrPC stabilized at high pressure (Kachel et al., BMC Struct Biol 6: 16). The results strongly suggest that the oligomeric form PrPoligo is in dynamic equilibrium with the monomeric forms via PrPC*, namely huPrP(C) reversible arrow huPrP(C)* reversible arrow huPrP(oligo).