Species-specific Differences in the Intermediate States of Human and Syrian Hamster Prion Protein Detected by High Pressure NMR Spectroscopy

Reversible monomer-oligomer transition in human prion protein

“…5C) in that it contains signals of monomeric PrP in a substantial amount, which are characteristic of the native states N 1 and N 2 described earlier. 8,10 Even after 9.5 h its concentration has not changed, indicating that PrP in these native ground states (we collectively call huPrP C ) is not directly involved in the formation of oligomers. At ambient pressure the excited states I 1 and I 2 and it is likely that these residues are mainly responsible for this broad component.…”

“…5B). 8,10 A reduction of the pressure to 0.3 MPa leads to a spectrum (Fig. 5E) that differs from the original low pressure spectrum (Fig.…”

“…The preparation of β-form of huPrP C (23-231) followed the procedure of Jackson (we collectively call huPrP C* ) are quite rare with relative concentrations of 0.02 and 0.0005. 10 By combining the two equilibria, the minimum equilibrium scheme for the oligomerization is represented by huPrP C  huPrP C*  huPrP oligo (Scheme 1).…”

“…Besides the stable structure (PrP C ) in solution, a meta-stable conformer (PrP C* ) exists, as a putative precursor to PrP Sc , in equilibrium with PrP C in human prion as well as in hamster prion as revealed from the high pressure NMR studies. [8][9][10] In fact, high pressure NMR allowed to identify two structural substates of the ground state PrP C (N 1 and N 2 ) and of the excited state PrP C* (I 1 and I 2 ) simultaneously occurring at ambient pressure with the relative concentrations of 0.762, 0.226, 0.011, 0.0005, respectively. However, there has been little structural information on the oligomeric forms of prion, despite the increasing demand for it.…”

Distinct Conformational States of the Alzheimer β‐Amyloid Peptide Can Be Detected by High‐Pressure NMR Spectroscopy

“…Communications a sequence-specific distribution of the thermodynamic parameters is observed usually in proteins (see for example, the pressure response of the human prion protein reported by Kremer et al [24] ). In addition, the accuracy of the thermodynamic parameters obtained from a fit of the data also strongly depends on the magnitude of chemical shift changes.…”