STRUCTURE OF THE RECOMBINANT FULL-LENGTH HAMSTER PRION PROTEIN PRP(29-231) - THE N-TERMINUS IS HIGHLY FLEXIBLE

The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrPC to the infecti ous scrapie form PrPSc; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these dise ases develop. In this study, the secondary structure of the recombinan t Syrian hamster PrP of residues 29-231 [PrP(29-231)] is investigated by multidimensional heteronuclear NMR. Chemical shift index analysis a nd nuclear Overhauser effect data show that PrP(29-231) contains three helices and possibly one short beta-strand, Most striking is the rand om-coil nature of chemical shifts for residues 30-124 in the full-leng th PrP. Although the secondary structure elements are similar to those found in mouse PrP fragment PrP(121-231), the secondary structure bou ndaries of PrP(29-231) are different from those in mouse PrP(121-231) but similar to those found in the structure of Syrian hamster PrP(90-2 31). Comparison of resonance assignments or PrP(29-231) and PrP(90-231 ) indicates that there may be transient interactions between the addit ional residues and the structured core. Backbone dynamics studies done by using the heteronuclear [H-1]-N-15 nuclear Overhauser effect indic ate that almost half of PrP(29-231), residues 29-124, is highly flexib le. This plastic region could feature in the conversion of PrPC to PrP Sc by template-assisted formation of beta-structure.