Cryo-EM structure of an amyloid fibril from systemic amyloidosis

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Journal Article

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Not refereed



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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.