6MST

Cryo-EM structure of human AA amyloid fibril

Summary for 6MST

• Entry DOI: 10.2210/pdb6mst/pdb
• EMDB information: 9232
• Descriptor: Serum amyloid A-1 protein (1 entity in total)
• Functional Keywords: aa-amyloidosis, serum amyloid a, cross-beta, helical, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 89773.85

Authors

Loerch, S.,Rennegarbe, M.,Liberta, F.,Grigorieff, N.,Fandrich, M.,Schmidt, M. (deposition date: 2018-10-18, release date: 2019-03-13, Last modification date: 2024-03-13)

Primary citation

Liberta, F.,Loerch, S.,Rennegarbe, M.,Schierhorn, A.,Westermark, P.,Westermark, G.T.,Hazenberg, B.P.C.,Grigorieff, N.,Fandrich, M.,Schmidt, M.
Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids.
Nat Commun, 10:1104-1104, 2019

PubMed Abstract: 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.

PubMed: 30846696
DOI: 10.1038/s41467-019-09033-z

Experimental method

ELECTRON MICROSCOPY (2.7 Å)