NMR structure of the bovine prion protein

The NMR structures of the recombinant 217-residue polypeptide chain C-termi nal fragment, bPrP(121-230). include a globular domain extending from resid ue 125 to residue 227. a short flexible chain end of residues 228-230, and an N-terminal flexibly disordered "tail" comprising 108 residues for the in tact protein and 4 residues for bPrP(121-230), respectively. The globular d omain contains three alpha-helices comprising the residues 144-154, 173-194 and 200-226, and a short antiparallel beta-sheet comprising the residues 1 28-131 and 161-164. The best-defined parts of the globular domain are the c entral portions of the helices 2 and 3. which are linked by the only disulf ide bond in bPrP. Significantly increased disorder and mobility is observed for helix 1. the loop 166-172 leading from the beta-strand 2 to helix 2, t he end of helix 2 and the following loop, and the last turn of helix 3. Alt hough there are characteristic local differences relative to the conformati ons of the murine and Syrian hamster prion proteins, the bPrP structure is essentially identical to that of the human prion protein. On the other hand , there are differences between bovine and human PrP in the surface distrib ution of electrostatic charges, which then appears to be the principal stru ctural feature of the "healthy" PrP form that might affect the stringency o f the species barrier for transmission of prion diseases between humans and cattle.