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Can motional dynamics account for the cytotoxicity of beta amyloid oligomers?

Yeh, C.-T.; Chang, H.-W.; Hsu, W.-H.; Huang, S.-J.; Wu, M.-H.; Tu, L.-H.; Lee, M.-C.; Chan, C. C. J.

2023-05-05 biophysics
10.1101/2023.05.04.539338 bioRxiv
Show abstract

The underlying biophysical principle governing the cytotoxicity of the oligomeric aggregates of {beta}-amyloid (A{beta}) peptides has long been an enigma. Here we show that the size of A{beta}40 oligomers can be actively controlled by incubating the peptides in reverse micelles. Our approach allowed for the first time a detailed comparison of the structures and dynamics of two A{beta}40 oligomers of different size, viz., 10 and 23 nm, by solid-state NMR. From the chemical shift data, we infer that the conformation of the residues from K16 to K28 are different between the 10-nm and 23-nm oligomers. We find that the 10-nm oligomers are more cytotoxic, and the molecular motions of their charged residues are more dynamic. Interestingly, the residue A21 exhibits an unusually high structural rigidity. Our data raise the interesting possibility that the cytotoxicity of A{beta}40 oligomers could also be correlated to the motional dynamics of the charged residues.

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