title: [Alpha-helix retention in prion proteins].
abstract: Prion diseases belong to a group of neurodegenerative disorders caused by conformational 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 prion proteins are not too conserved judging from the evolutionary rates, conserved 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-step substitutions in human PrP sequences. The data obtained support a suggestion that prion diseases result from changes in PrP conformation manifested in destroying the alpha-helices and formation of beta-structures.
authors.affiliation: Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: I B
authors.initials: IB
authors.lastname: Kuznetsov
authors.forename: P S
authors.initials: PS
authors.lastname: Morozov
authors.forename: Iu G
authors.initials: IuG
authors.lastname: Matushkin
mesh_terms: D019943:Amino Acid Substitution; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D011328:Prions
vernacular_title: Sokhranenie al'fa-spiraleĭ v prionovykh belkakh.