Mechanism of amyloid beta-protein dimerization determined using single-molecule AFM force spectroscopy

作者：Lv Zhengjian; Roychaudhuri Robin; Condron Margaret M; Teplow David B; Lyubchenko Yuri L^*

来源：Scientific Reports, 2013, 3: 2880.

DOI：10.1038/srep02880

A beta 42 and A beta 40 are the two primary alloforms of human amyloid beta-protein (A beta). The two additional C-terminal residues of A beta 42 result in elevated neurotoxicity compared with A beta 40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for A beta 42 and A beta 40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of A beta 42 and A beta 40 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 A beta peptide aggregation. These novel properties of A beta 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.

• 出版日期2013-10-7