X-ray Crystallography Reveals Parallel and Antiparallel β-Sheet Dimers of a β-Hairpin Derived from Aβ_16–36 that Assemble to Form Different Tetramers

Abstract

Supporting Table Table S1. Crystallographic properties, crystallization conditions, and data collection and model refinement statistics for peptide 1. S2 Materials and Methods General information. S3 Synthesis of peptide 1. S3 Crystallization procedure for peptide 1. S5 X-ray crystallographic data collection, data processing, and structure determination for peptide 1. S6 Preparation of Aβ 40 and Aβ 42 oligomers S7 SDS-PAGE and silver staining. S8 Replica exchange molecular dynamics (REMD). S9 References and Notes S10

Surface-induced dissociation of protein complexes on a cyclic ion mobility spectrometer

“…We have recently begun characterizing aggregates of synthetic covalent 'Trimers' derived from Aβ 17-36 , which have been pioneered and characterized by the Nowick laboratory. 33,[61][62][63] A summary of the wide variety of Aβ-derived β-hairpin rich molecules synthesized by the Nowick laboratory is available. 64 Briefly, the 'Trimer' peptides, such as the model molecule Trimer 1 N-Me investigated here (shown in Scheme S1 †), consist of three β-hairpin peptides derived from Aβ 17-36 and covalently linked by disulfide bonds.…”

Formaldehyde‐Crosslinked Nontoxic Aβ Monomers to Form Toxic Aβ Dimers and Aggregates: Pathogenicity and Therapeutic Perspectives

“…The 3D structure of the Aβ 16‐36 trimer (PDB: 5w4i) is composed of three molecules of Aβ monomers with trans ‐parallel β‐sheets [71] . AβO channels, for example Aβ*56, forma hole or pore with four trimers [62,67] . Moreover, fibrils (PDB: 5kk3) are mainly made of massive dimers with cis ‐parallel β‐sheets, [72] supporting the notion that the Aβ dimer is the basic unit.…”

“…[71] AβO channels, for example Aβ*56, forma hole or pore with four trimers. [62,67] Moreover, fibrils (PDB: 5kk3) are mainly made of massive dimers with cis-parallel β-sheets, [72] supporting the notion that the Aβ dimer is the basic unit.…”

“…The crystal structure of the Aβ monomer(PDB: 1iyt) exhibits an α‐helix and β‐turn [65] . Notably, the Aβ dimer (PDB: 5aef) is made of two trans ‐ or cis ‐parallel β‐sheets [66,67] . Further, trans ‐parallel β‐sheets of the Aβ monomer contribute to oligomer formation, while cis ‐parallel β‐sheets promote non‐water‐soluble fibril formation [68–70] .…”

“…[65] Notably, the Aβ dimer (PDB: 5aef) is made of two trans-or cis-parallel β-sheets. [66,67] Further, trans-parallel β-sheets of the Aβ monomer contribute to oligomer formation, while cis-parallel β-sheets promote nonwater-soluble fibril formation. [68][69][70] A 7.3 nm peptide chain of the Aβ42 trimer was found to be longer than that of Aβ40 (5.3 nm); therefore, the former more easily formed fibrils than the latter.…”