High-resolution structure of monomorphic Aβ_1-40 fibrils.

Authors

Salima Bahri, Ravi Shankar Palani, Robert Silvers, Brian Michael, Veronica Lattanzi, Ingemar André, Sara Linse, Robert G Griffin

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 28. Pages e2603575123. Jul 14, 2026. Epub Jul 08, 2026.

Abstract

Amyloid-β (Aβ) fibrils primarily composed of Aβ_1-40 and Aβ_1-42 form the core of senile plaques in Alzheimer's disease. Aβ_1-40 fibrils may exhibit significant polymorphism influenced by sample preparation conditions, complicating atomic resolution structural characterization. To establish a reliable structural baseline, we developed a protocol for expressing and purifying recombinant Aβ_1-40 that forms monomorphic fibrils under physiological conditions (pH 7.4). We present a high-resolution structure of these unseeded, monomorphic Aβ_1-40 fibrils obtained using magic-angle spinning NMR spectroscopy (PDB ID 12GB). We obtained unambiguous chemical shift assignments for approximately 90% of the residues and measured over 500 distance and torsion angle restraints. The resolved structure, with a backbone RMSD of 0.63 ± 0.06 Å, shows two monomers per filament plane, with two distinct β-sheets (residues E11-E22 and K28-V39, respectively) running along the fibril axis with H-bonding between each plane, and the two strands linked by a flexible loop region. This structure reveals three continuous hydrophobic cores inside each filament which bury 24 hydrophobic side chains per filament plane: those of L17, F19, A21, V24, A30, I32, M35, V40 between the two β-strands within each monomer and I31, L34, V36, V39 between the two monomers. Small angle X-ray scattering reveals the size and geometry of the fibril cross-section, which is compatible with a two-filament arrangement with a total of 4 monomers per fibril plane.

PMID:
42418485
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.