Alpha-helix retention in prion proteins

Prion diseases belong to a group of neurodegenerative disorders caused by c onformational changes-destroying the alpha-helices-in prion proteins (PrP). We performed a phylogenetic analysis of 32 PrP sequences and restored the most probable evolutionary spectrum of amino acid substitutions. Although p rion proteins are not too conserved judging from the evolutionary rates, co nserved substitutions leading only to amino acids with similar physical and chemical parameters occurred in evolution within the putative helical PrP regions. Those substitutions that destroy alpha-helices primarily arose in prion proteins as was demonstrated by the methods of prediction of protein secondary structure used for analysis of the complete spectrum of single-st ep substitutions in human PrP sequences. The data obtained support a sugges tion that prion diseases result from changes in PrP conformation manifested in destroying the alpha-helices and formation of beta-structures.