NR AXXQ
AU Teruya,K.; Yamada,Y.; Nishimura,T.; Suda,Y.; Doh-ura,K.
TI Characterization of the Interaction between Prion Protein and Heparin
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.56
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Interaction between prion protein and endogenous glycosaminoglycans on the cell surface is proposed to play a key role in the infection and transmission of the prion, since sulfated glycans such as heparin and pentsan polysulfate (PPS) exert anti-prion activities by competitively inhibiting the interaction. However, interaction between prion protein and sulfated glycans is not fully evaluated. In this report, interaction between prion protein and heparin as a representative sulfated glycan was investigated to clarify which structural unit in heparin is responsible for the binding of prion protein, and which region of prion protein is responsible for the binding.
Heparin is heterogeneous in composition and chain length, but there are a few known methods to destruct the partial structure of heparin specifically. Comparison of the anti-prion activities of the modified heparin prepared by two different methods revealed that a certain disaccharide unit is essential to the potency for inhibiting PrPres formation in prion-infected cells. Then, "Sugar Chip" was prepared by immobilizing the disaccharide unit on a sensor chip to investigate the interaction with prion protein using surface plasmon resonance (SPR) technique. Because recombinant prion protein, murine rPrP23-231, exhibited a significant binding profile on the Sugar Chip, truncated domains of the recombinant prion protein were tested for their binding to the Sugar Chip. It was found that N-terminal domain of prion protein, 23-89, was necessary for the interaction with the disaccharide unit in heparin. Finally, SPR analysis revealed that the interaction between the N-terminal domain of prion protein and the disaccharide unit was competitively inhibited by PPS. These results suggest that the SPR-based assay system composed of the prion protein and the Sugar Chip might be utilized as either a facile anti-prion chemical screening method or a research tool to investigate the mechanism of anti-prion chemicals.
AD K. Teruya, Y. Yamada, K. Doh-ura, Tohoku University, Graduate School of Medicine, Japan; T. Nishimura, SUDx-Biotech Corp., Japan; Y. Suda, Kagoshima University, Graduate School of Science and Engineering, Japan
SP englisch
PO Schottland