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Cryo-EM structure of an amyloid fibril from systemic amyloidosis

TitleCryo-EM structure of an amyloid fibril from systemic amyloidosis
Publication TypeJournal Article
Year of Publication2018
AuthorsLiberta, F, Loerch S, Rennegarbe M, Schierhorn A, Westermark P, Westermark GT, Grigorieff N, Fändrich M, Schmidt M

Systemic AA amyloidosis is a worldwide occurring disease of humans and animals that arises from the misfolding of serum amyloid A protein. To provide insights into the molecular basis of this disease we used electron cryo-microscopy and determined the structure of an ex vivo amyloid fibril purified from AA amyloidotic mice at 3.0 A resolution. The fibril consists of C-terminally truncated serum amyloid A protein arranged into a compactly folded all-beta conformation. The structure identifies the protein N-terminus as central for the assembly of this fibril and provides a mechanism for its prion-like replication. Our data further explain how amino acid substitutions within the tightly packed fibril core can lead to amyloid resistance in vivo.

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