Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids

被引：0
作者：
Falk Liberta
Sarah Loerch
Matthies Rennegarbe
Angelika Schierhorn
Per Westermark
Gunilla T. Westermark
Bouke P. C. Hazenberg
Nikolaus Grigorieff
Marcus Fändrich
Matthias Schmidt
机构：
[1] Ulm University,Institute of Protein Biochemistry
[2] Howard Hughes Medical Institute,Janelia Research Campus
[3] Martin-Luther-University,Institute of Biochemistry and Biotechnology
[4] Uppsala University,Department of Immunology, Genetics, and Pathology
[5] Uppsala University,Department of Medical Cell Biology
[6] University of Groningen,Department of Rheumatology & Clinical Immunology
[7] University Medical Center Groningen,undefined
来源：
Nature Communications | / 10卷
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摘要：
Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 Å and 2.7 Å for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-β sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar β-arch conformations within the N-terminal ~21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest strategies of combating this disease by interfering with specific fibril polymorphs.
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