Molecular structure of an N-terminal phosphorylated β-amyloid fibril

Significance This work reports the molecular structure formed by a pathologically relevant posttranslational modified β-amyloid (Aβ), the Ser-8-phosphorylated Aβ40 (pS8-Aβ40 ). The N-terminal structures in pS8-Aβ40 fibril differ significantly from all known wild-type Aβ40 fibrils, with strong intra-strand interactions that make the N terminus associated closely with the amyloid core. The pS8-Aβ40 fibril possesses strong cross-seeding ability to wild-type Aβ40 monomers, while the propagated fibrillar structure shows higher thermodynamic stability and core rigidity compared to the fibrils formed by the self-nucleation of wild-type Aβ40 . Our finding may shed light on the origin of structural polymorphisms in Aβ amyloids.