Kreutzer, Adam G. Hamza, Imane L. Spencer, Ryan K. Nowick, James S. X‑ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ<sub>17–36</sub> β‑Hairpin 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 paper 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. Two covalent constraints act in tandem to stabilize the Aβ<sub>17–36</sub> peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29. An <i>N</i>-methyl group at position 33 blocks uncontrolled aggregation. 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. β- hairpin;covalent constraints act;annular pore;intramolecular disulfide linkage;β- hairpin monomers;position 33 blocks;oligomer;β- amyloid peptide;20- residue peptide segment 2016-03-11
    https://acs.figshare.com/articles/dataset/X_ray_Crystallographic_Structures_of_a_Trimer_Dodecamer_and_Annular_Pore_Formed_by_an_A_sub_17_36_sub_Hairpin/3125845
10.1021/jacs.6b01332.s009