PT - JOURNAL ARTICLE AU - Falk Liberta AU - Sarah Loerch AU - Matthies Rennegarbe AU - Angelika Schierhorn AU - Per Westermark AU - Gunilla T. Westermark AU - Nikolaus Grigorieff AU - Marcus Fändrich AU - Matthias Schmidt TI - Cryo-EM structure of an amyloid fibril from systemic amyloidosis AID - 10.1101/357129 DP - 2018 Jan 01 TA - bioRxiv PG - 357129 4099 - http://biorxiv.org/content/early/2018/06/29/357129.short 4100 - http://biorxiv.org/content/early/2018/06/29/357129.full AB - 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 Å resolution. The fibril consists of C-terminally truncated serum amyloid A protein arranged into a compactly folded all-β 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.