NR ADPE
AU Downing,D.T.; Lazo,N.D.
TI Molecular modelling indicates that the pathological conformations of prion proteins might be beta-helical
QU Biochemical Journal 1999 Oct 15; 343 Pt 2: 453-60
PT journal article
AB Creutzfeldt-Jakob disease, kuru, scrapie and bovine spongiform encephalopathy are diseases of the mammalian central nervous system that involve the conversion of a cellular protein into an insoluble extracellular isoform. Spectroscopic studies have shown that the precursor protein contains mainly alpha-helical and random-coil conformations, whereas the prion isoform is largely in the beta conformation. The pathogenic prion is resistant to denaturation and protease digestion and can promote the conversion of the precursor protein to the pathogenic form. These properties have yet to be explained in terms of the structural conformations of the proteins. In the present study, molecular modelling showed that prion proteins could adopt the beta-helical conformation, which has been established for a number of fibrous proteins and has been suggested previously as the basis of amyloid fibrils. The beta-helical conformation provides explanations for the biophysical and biochemical stability of prions, their ability to form templates for the transmission of pathological conformation, and the existence of phenotypical strains of the prion diseases.
MH Amino Acid Sequence; Animal; Circular Dichroism; Human; Hydrogen Bonding; *Models, Molecular; Molecular Sequence Data; Mutation; Peptide Fragments/chemical synthesis/chemistry/genetics/metabolism; Prion Diseases/genetics/*metabolism/pathology/transmission; Prions/*chemistry/genetics/*metabolism; Protein Binding; Protein Folding; Protein Isoforms/chemistry/genetics/metabolism; Protein Structure, Secondary; Repetitive Sequences, Amino Acid; Structure-Activity Relationship
AD Marshall Research Laboratories, Department of Dermatology, University of Iowa College of Medicine, Coralville, IA 52241-8802, USA. donald-downing@uiowa.edu
SP englisch
PO England