PRNP and prion disease: Given the effect of the V127 polymorphism on the PrP β-sheet backbone geometry and intermolecular association of PrP monomers observed here, it is tempting to speculate that dimerisation via the formation of the intermolecular PrP β-sheet may be a critical event in PrP oligomerisation and prion propagation and thus explain the exceptional effect of the residue 127 polymorphism on human prion disease.