Journal
PRION
Volume 2, Issue 3, Pages 118-122Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/pri.2.3.7148
Keywords
human prion; oligomer structure; pressure dissociation; reversible monomer-oligomer transition; circular dichroism; high pressure NMR; atomic force microscopy
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Funding
- MAFF (The Ministry of Agriculture, Forestry and Fisheries of Japan)
- MEXT (the Ministry of Education, Culture, Sports, Science and Technology of Japan) [16370054]
- DFG
- Grants-in-Aid for Scientific Research [16370054] Funding Source: KAKEN
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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).
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