We obtained cryo-EM structure of amyloid fibrils from three different forms of systemic amyloidosis: AA (Liberta F, Loerch S, Rennegarbe M et al., Nature Comm. 10, 1104, 2019), AL (Radamaker et al., Nature Comm. 10, 1103, 2019) and ATTR (Schmidt M et al. Nature Comm. 10, 5008, 2019). In addition, we obtained the structure of Aβ amyloid fibrils from Alzheimer’s disease/cerebral amyloid angiopathy (Kollmer M et al. Nature Comm. 10, 4760, 2019). Our data reveal the present of right-hand twisted cross-β sheets and provide, in specific cases, evidence about the order of events during fibril formation, such as whether proteolysis precedes fibril formation or vice versa. Amyloid fibrils from patient tissue are structurally different from known amyloid-like fibrils formed in vitro. Our findings illuminate the structural repertoire of protein aggregates, provide insights into the mechanism of fibril formation in vivo, and inform about potential therapeutic strategies.

Cryo-electron microscopy structures of amyloid fibrils

ACS Spring Meeting 2021

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