Mechanism of amyloid β-protein dimerization determined using single-molecule AFM force spectroscopy.
Document Type
Article
Journal Title
Scientific Reports
Publication Date
Fall 10-7-2013
Volume
3
Abstract
Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding as N-terminal was considered as disordered segment with no effect on the Aβ peptide aggregation. These novel properties of Aβ proteins suggests that the stabilization of N-terminal interactions is a switch in redirecting of amyloids form the neurotoxic aggregation pathway, opening a novel avenue for the disease preventions and treatments.
MeSH Headings
Amyloid beta-Peptides, Humans, Microscopy, Atomic Force, Protein Folding, Protein Multimerization
DOI Link
ISSN
2045-2322
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Recommended Citation
Lv, Zhengjian; Roychaudhuri, Robin; Condron, Margaret M.; Teplow, David B.; and Lyubchenko, Yuri L., "Mechanism of amyloid β-protein dimerization determined using single-molecule AFM force spectroscopy." (2013). Journal Articles: Pharmaceutical Sciences. 9.
https://digitalcommons.unmc.edu/cop_pharmsci_articles/9