Abstract
Soluble oligomers and protofibrils of the Aβ42 peptide are neurotoxic intermediates in the conversion of monomeric Aβ42 into the amyloid fibrils associated with Alzheimer's disease. Nuclear magnetic resonance and Fourier transform infrared spectroscopy, along with single-touch atomic force microscopy, are used to establish the structural transitions involved in fibril formation. We show that under conditions favorable for the nucleated conformation conversion, the Aβ42 peptide aggregates into largely unstructured low-molecular weight (MW) oligomers that are able to stack to form high-MW oligomers and to laterally associate to form protofibrils. β-Sheet secondary structure develops during the irreversible lateral association of the oligomers. The first step in this conversion is the formation of an antiparallel β-hairpin stabilized by intramonomer hydrogen bonding. The antiparallel β-hairpins then associate into a cross β-sheet structure with parallel and in-register β-strands having intermonomer hydrogen bonding.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
