Study of alpha-helix to beta-strand to beta-sheet transitions in amyloid: the role of segregated hydrophobic beta-strands.
A conformational analysis including three polypeptide chains known to be amyloidogenic and neurotoxic has shown the occurrence of low probability hydrophobic beta-strands stabilized by intramolecular interactions. It is argued that by engaging in non-bonded and hydrophobic interactions these beta-strands seed the assembly of beta-sheets in amyloid fibrils following a non-cooperative mechanism dissimilar to beta-sheet folding in proteins. Molecular models of amyloid fibrils formed by such beta-strand templates were built. It is shown that the parallel alignment of beta-strands creates an extensive hydrophobic surface whereas the antiparallel alignment causes the formation of hydrophobic and hydrophilic aggregates. A comparison with experimental data and previous calculations is established.
Jacchieri
S G
SG
Fundação Antônio Prudente, Sao Paulo, Brazil.
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
D000682:Amyloid; D016229:Amyloid beta-Peptides