Soluble zinc-induced amyloid β oligomers probed through fluorine NMR spectroscopy.

Authors

Luigi Russo, Kalyan S Chakrabarti, Robin Backer, Kerstin Overkamp, Serge Gambarelli, Dieter Willbold, Giuseppe Sicoli, Nasrollah Rezaei-Ghaleh

Published in

Communications chemistry. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Divalent zinc ions (Zn) interact with amyloid β (Aβ) peptides and influence its Alzheimer disease (AD)-related aggregation. Little is known about the structural properties of Zn-induced Aβ oligomers. Here, we report recombinant production of fluorinated Aβ40 at Phe4, Tyr10, Phe19 and Phe20 residues and utilize these fluorinated residues as proxies to interrogate Zn-induced Aβ40 oligomers. Our NMR and CW EPR results confirm Zn binding to the N-terminal region of Aβ40 and demonstrate the reversible oligomerization and irreversible aggregation of Aβ40 upon Zn addition. The ¹⁹F NMR relaxation and dark-state exchange saturation transfer (DEST) data provide dynamical information on free Aβ40 and demonstrate that monomeric Aβ40 is in exchange with small Zn-induced Aβ40 oligomers with less than about 60 kDa molecular weight on a millisecond timescale. The ¹⁹F ENDOR data suggest that the distance between the N-terminally attached nitroxide spin and fluorinated residues within the Zn-Aβ40 aggregates is larger than about 1.5 nm. Our results shed light on the properties of soluble Zn-induced Aβ oligomers and pave the way for further structural characterization of these Aβ aggregates.

PMID:
42443333
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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