NR AEQX
AU Goldfarb,L.G.; Brown,P.; Haltia,M.; Ghiso,J.; Frangione,B.; Gajdusek,D.C.
TI Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils
QU Proceedings of the National Academy of Sciences of the United States of America 1993 May 15; 90(10): 4451-4
PT journal article
AB We synthesized polypeptides corresponding to sequences encoded by normal and mutant alleles in the regions of codon 178 (Asp -> Asn) and codon 200 (Glu -> Lys) of the chromosome 20 amyloid gene that have been linked to familial Creutzfeldt-Jakob disease. Peptide suspensions from both regions spontaneously formed amyloid fibrils with different morphological characteristics and aggregation tendencies. Fibrillar arrays were denser and more profuse in mutant than in normal peptide suspensions and were even more marked when the homologous mutant and normal peptides were mixed together. Preparations from the region of codon 200 were in all cases more fibrillogenic than corresponding peptides from the region of codon 178. These in vitro observations support the hypothesis that amino acid changes from pathogenic single-allele point mutations in Creutzfeldt-Jakob disease may nucleate the in vivo folding behavior of the normal host protein to favor formation of insoluble amyloid fibrils.
MH Amino Acid Sequence; Amyloid beta-Protein Precursor/*chemistry/metabolism; Creutzfeldt-Jakob Syndrome/*genetics/pathology; Human; Macromolecular Systems; Microscopy, Electron; Molecular Sequence Data; Point Mutation; Protein Binding; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.
AD Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
SP englisch
PO USA