title: Effect of the amyloid β hairpin's structure on the handedness of helices formed by its aggregates.
abstract: Various structural models for amyloid β fibrils have been derived from a variety of experimental techniques. However, these models cannot differentiate between the relative position of the two arms of the β hairpin called the stagger. Amyloid fibrils of various hierarchical levels form left-handed helices composed of β sheets. However it is unclear if positive, negative and zero staggers all form the macroscopic left-handed helices. To address this issue we have conducted extensive molecular dynamics simulations of amyloid β sheets of various staggers and shown that only negative staggers lead to the experimentally observed left-handed helices while positive staggers generate the incorrect right-handed helices. This result suggests that the negative staggers are physiologically relevant structure of the amyloid β fibrils.
authors.affiliation: Computational Biology and Bioinformatics Group, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. pkc@ornl.gov
authors.forename: Pavan K
authors.initials: PK
authors.lastname: GhattyVenkataKrishna
authors.forename: Edward C
authors.initials: EC
authors.lastname: Uberbacher
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides
keywords: Alzheimer’s; Amyloid; Protein structure