Structural highlights
Disease
[SAA2_MOUSE] Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.
Function
[SAA2_MOUSE] Major acute phase reactant. Apolipoprotein of the HDL complex.
Publication Abstract from PubMed
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 A and 2.7 A 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-beta sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar beta-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.
Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids.,Liberta F, Loerch S, Rennegarbe M, Schierhorn A, Westermark P, Westermark GT, Hazenberg BPC, Grigorieff N, Fandrich M, Schmidt M Nat Commun. 2019 Mar 7;10(1):1104. doi: 10.1038/s41467-019-09033-z. PMID:30846696[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liberta F, Loerch S, Rennegarbe M, Schierhorn A, Westermark P, Westermark GT, Hazenberg BPC, Grigorieff N, Fandrich M, Schmidt M. Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids. Nat Commun. 2019 Mar 7;10(1):1104. doi: 10.1038/s41467-019-09033-z. PMID:30846696 doi:http://dx.doi.org/10.1038/s41467-019-09033-z
