Reversible monomer-oligomer transition in human prion protein |
| |
| Authors: | Ken Sasaki Jyoti Gaikwad Shuhei Hashiguchi Toshiya Kubota Kazuhisa Sugimura Werner Kremer Hans Robert Kalbitzer Kazuyuki Akasaka |
| |
| Affiliation: | 1High Pressure Protein Research Center; Institute of Advanced Technology and Graduate School of Biology-Oriented Science and Technology; Kinki University; Kinokawa, Japan;2Department of Bioengineering; Faculty of Engineering; Kagoshima University; Kagoshima, Japan;3Institute for Biophysics and Physical Biochemistry; University of Regensburg; Regensburg, Germany |
| |
| Abstract: | The structure and the dissociation reaction of oligomers PrPoligo from reduced human prion huPrPC(23–231) have been studied by 1H-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The 1H-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∼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 huPrPC ⇆ huPrPC* ⇆ huPrPoligo.Key words: human prion, oligomer structure, pressure dissociation, reversible monomer-oligomer transition, circular dichroism, high pressure NMR, atomic force microscopy |
| |
| Keywords: | |
|
|
