NR ATRM
AU Kremer,W.; Kachel,N.; Kalbitzer,H.R.
TI Observation of intermediate states of the human prion protein by high pressure NMR
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-28
PT Konferenz-Poster
AB Conformational intermediates of the human prion protein huPrP were characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the pressure response between N-terminal truncated huPrP(121-230) and the full length huPrP(23-230). High-pressure resonance indicates that the folded core of the human prion protein occurs in two structural states N1 and N2 in solution associated with rather small differences in free enthalpies (3.2 kJ/mol). At atmospheric pressure approximately 22% of the protein are already in the pressure favored conformation N2. There is a second process representing a possible folding intermediate I with average free enthalpies of 14.2 kJ/mol which could represent a preaggregation state of the protein. The most pressure-sensitive region is the loop between beta-strand 1 and alpha-helix 1, indicating that this region might be the first entry point for the infectious conformer to convert the cellular protein.
AD Wener Kremer, Norman Kachel, Hans Robert Kalbitzer, University of Regensburg, Germany
SP englisch
PO Deutschland