RT Journal Article
SR Electronic
T1 Cryo-EM structure of an amyloid fibril from systemic amyloidosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 357129
DO 10.1101/357129
A1 Falk Liberta
A1 Sarah Loerch
A1 Matthies Rennegarbe
A1 Angelika Schierhorn
A1 Per Westermark
A1 Gunilla T. Westermark
A1 Nikolaus Grigorieff
A1 Marcus Fändrich
A1 Matthias Schmidt
YR 2018
UL http://biorxiv.org/content/early/2018/06/29/357129.abstract
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.