Reversible monomer-oligomer transition in human prion protein.
The structure and the dissociation reaction of oligomers Pr(Poligo) from reduced human prion huPrP(C)(23-231) have been studied by (1)H-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 approximately 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 PrP(C*), a rare metastable form of PrP(C) stabilized at high pressure (Kachel et al., BMC Struct Biol 6:16). The results strongly suggest that the oligomeric form PrP(oligo) is in dynamic equilibrium with the monomeric forms via PrP(C*), namely huPrP(C)[left arrow over right arrow]huPrP(C*)[left arrow over right arrow]huPrP(oligo).
Sasaki
Ken
K
High Pressure Protein Research Center, Institute of Advanced Technology and Graduate School of Biology-Oriented Science and Technology, Kinki University, Kinokawa, Japan.
Gaikwad
Jyoti
J
Hashiguchi
Shuhei
S
Kubota
Toshiya
T
Sugimura
Kazuhisa
K
Kremer
Werner
W
Kalbitzer
Hans Robert
HR
Akasaka
Kazuyuki
K
D002942:Circular Dichroism; D005453:Fluorescence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D010084:Oxidation-Reduction; D018621:PrPC Proteins / Q000737:chemistry* / Q000648:ultrastructure; D011312:Pressure; D020836:Protein Structure, Quaternary; D013696:Temperature; D014364:Tryptophan
D018621:PrPC Proteins; D014364:Tryptophan