A new amyloid-like beta-aggregate with amyloid characteristics, except fibril morphology.
Amyloid plaques, formed from amyloid beta (Abeta) peptides (mainly Abeta40 or Abeta42), are one of the most important pathological characteristics of Alzheimer's disease. Here, a single D-form proline substitution in the 40-amino-acid Abeta40 peptide can totally change the aggregation behavior of this peptide. The residue immediately preceding each glycine in Abeta40 (S8, V24, I32, and V36) was individually replaced by D-form proline ((D)Pro). The resulting (D)P-G sequence (the (D)Pro residue and the following Gly residue) was designed as a "structural clip" to force the formation of a bend in the peptide, as this sequence has been reported to be a strong promoter of beta-hairpin formation. The mutant peptide with Val24-to-(D)Pro substitution, named V24P, formed a new amyloid-like beta-aggregate at high peptide concentration. The aggregate has most of the characteristics of amyloid fibrils, except fibril morphology. Moreover, the mutant peptide V24P, when mixed with Abeta40, can attenuate the cytotoxicity of Abeta40.
Chang
Evan S-H
ES
Institute of Biological Chemistry, Academia Sinica, No. 128, Sec 2, Academia Road, Nankang, Taipei 115, Taiwan, ROC.
Liao
Tai-Yan
TY
Lim
Tsong-Shin
TS
Fann
Wunshain
W
Chen
Rita P-Y
RP
D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology / Q000648:ultrastructure; D000818:Animals; D052160:Benzothiazoles; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003224:Congo Red; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011392:Proline / Q000235:genetics; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors; D014633:Valine / Q000235:genetics
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D050505:Mutant Proteins; D010455:Peptides; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red; D011392:Proline; D014633:Valine