Oligomerizaiton and fibril asssembly of the amyloid-beta protein.
In this chapter, we attempt to analyze the evolution of the amyloid-beta (Abeta) molecular structure from its inception as part of the Abeta precursor protein to its release by the secretases and its extrusion from membrane into an aqueous environment. Biophysical studies suggest that the Abeta peptide sustains a series of transitions from a molecule rich in alpha-helix to a molecule in which beta-strands prevail. It is proposed that initially the extended C-termini of two opposing Abeta dimers form an antiparallel beta-sheet and that the subsequent addition of dimers generates a helical Abeta protofilament. Two or more protofilaments create a strand in which the hydrophobic core of the beta-sheets is shielded from the aqueous environment by the N-terminal polar domains of the Abeta dimers. Once the nucleation has occurred, the Abeta filament grows in length by the addition of dimers or tetramers.
Roher
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AE
Haldeman Laboratory for Alzheimer's Disease Research, Sun Health Research Institute, Sun City, AZ 85351, USA. aroher@mail.sunhealth.org
Baudry
J
J
Chaney
M O
MO
Kuo
Y M
YM
Stine
W B
WB
Emmerling
M R
MR
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry; D019281:Dimerization; D010450:Endopeptidases / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016874:Neurofibrillary Tangles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D014961:X-Ray Diffraction
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009842:Oligopeptides; D010455:Peptides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human