Structural insights into the interaction between prion protein and heparin

Transmissible spongiform encephalopathies are caused by an abnormal isoform of the prion protein (PrP). Conversion of cellular PrP (PrPC) into the pathological conformer, PrPSc, involves contact between both isoforms and probably requires a cofactor, such as a glycosaminoglycan or a nucleic acid. It is known that PrP interacts with heparin (Hep), but little is known about the structural features of this interaction. In this work, we investigated the biophysical profile of the murine recombinant PrP (PrP 23‐231) interaction with Hep. We found that the Far‐UV CD ellipticity values from PrP 23‐231 decrease with increasing Hep concentrations, followed by a little increase in light scattering. These results suggest that Hep may induce partial unfolding leading to protein oligomerization. We also investigated the interaction of Hep with another PrP construct, lacking a portion of the N‐terminal domain (PrP Δ 51‐90). Hep caused no changes on PrP Δ51‐90 structure. These result indicates that Hep binding site in PrP 23‐231 is restricted from amino acid 51 to 90. In addition, we searched for Hep sulfation groups important for interaction using modified Heps. Heps containing only 6‐O‐sulfated or 2‐O‐sufated groups made no changes on the secondary structure of the prion protein. On this basis it may be inferred that these two sulfate groups play important role in prion‐heparin interaction. Support: CNPq, PRONEX, FAPERJ, FINEP.