In this chapter, we attempt to analyze the evolution of the amyloid-β (Aβ) molecular structure from its inception as part of the Aβ precursor protein to its release by the secretases and its extrusion from membrane into an aqueous environment. Biophysical studies suggest that the Aβ peptide sustains a series of transitions from a molecule rich in α-helix to a molecule in which β-strands prevail. It is proposed that initially the extended C-termini of two opposing Aβ dimers form an antiparallel β-sheet and that the subsequent addition of dimers generates a helical Aβ protofilament. Two or more protofilaments create a strand in which the hydrophobic core of the β-sheets is shielded from the aqueous environment by the N-terminal polar domains of the Aβ dimers. Once the nucleation has occurred, the Aβ filament grows in length by the addition of dimers or tetramers. Copyright (C) 2000 Elsevier Science B.V.
|Number of pages||13|
|Journal||Biochimica et Biophysica Acta - Molecular Basis of Disease|
|Publication status||Published - 2000 Jul 26|
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology