Beta Amyloid Oligomers with Higher Cytotoxicity have Higher Sidechain Dynamics

Author:

Yeh Chen‐Tsen1,Chang Han‐Wen1ORCID,Hsu Wen‐Hsin1,Huang Shing‐Jong2,Wu Meng‐Hsin3,Tu Ling‐Hsien3ORCID,Lee Ming‐Che1ORCID,Chan Jerry Chun Chung1ORCID

Affiliation:

1. Department of Chemistry National Taiwan University No. 1, Section 4, Roosevelt Road Taipei 10617 Taiwan

2. Instrumentation Center National Taiwan University No. 1, Section 4, Roosevelt Road Taipei 10617 Taiwan

3. Department of Chemistry National Taiwan Normal University No. 88, Section 4, Ting-Chow Road Taipei 11677 Taiwan

Abstract

AbstractThe underlying biophysical principle governing the cytotoxicity of the oligomeric aggregates of β‐amyloid (Aβ) peptides has long been an enigma. Here we show that the size of Aβ40 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 Aβ40 oligomers of different sizes, viz., 10 and 23 nm, by solid‐state NMR. From the chemical shift data, we infer that the conformation and/or the chemical environments 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 motion of the sidechain of its charged residue K16 is more dynamic. Interestingly, the residue A21 exhibits unusually high structural rigidity. Our data raise an interesting possibility that the cytotoxicity of Aβ40 oligomers could also be correlated to the motional dynamics of the sidechains.

Funder

Ministry of Science and Technology, Taiwan

Publisher

Wiley

Subject

General Chemistry,Catalysis,Organic Chemistry

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