High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies. This poster presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ. The development of a peptide, in which Aβ<sub>17–36</sub> is stabilized as a β-hairpin is described and the X-ray crystallographic structures of oligomers it forms are reported. The peptide readily crystallizes as a folded β-hairpin, which assembles hierarchically in the crystal lattice. Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore. This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore. This model may provide a better understanding of the molecular basis of Alzheimer’s disease at atomic resolution.

X-ray crystallographic structures of a trimer, dodecamer, and annular pore formed by an Aβ<sub>17–36</sub> β-hairpin

253rd National Meeting (2017)

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X-ray crystallographic structures of a trimer, dodecamer, and annular pore formed by an Aβ17–36 β-hairpin

X-ray crystallographic structures of a trimer, dodecamer, and annular pore formed by an Aβ_17–36 β-hairpin