AA amyloid fibrils from diseased tissue are structurally different from in vitro formed SAA fibrils.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 02 2021
Historique:
received: 04 09 2020
accepted: 07 01 2021
entrez: 13 2 2021
pubmed: 14 2 2021
medline: 3 3 2021
Statut: epublish

Résumé

Systemic AA amyloidosis is a world-wide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from serum amyloid A (SAA) protein. Using cryo electron microscopy we here show that amyloid fibrils which were purified from AA amyloidotic mice are structurally different from fibrils formed from recombinant SAA protein in vitro. Ex vivo amyloid fibrils consist of fibril proteins that contain more residues within their ordered parts and possess a higher β-sheet content than in vitro fibril proteins. They are also more resistant to proteolysis than their in vitro formed counterparts. These data suggest that pathogenic amyloid fibrils may originate from proteolytic selection, allowing specific fibril morphologies to proliferate and to cause damage to the surrounding tissue.

Identifiants

pubmed: 33579941
doi: 10.1038/s41467-021-21129-z
pii: 10.1038/s41467-021-21129-z
pmc: PMC7881110
doi:

Substances chimiques

Amyloid 0
Recombinant Proteins 0
Serum Amyloid A Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1013

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Auteurs

Akanksha Bansal (A)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Matthias Schmidt (M)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Matthies Rennegarbe (M)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Christian Haupt (C)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Falk Liberta (F)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Sabrina Stecher (S)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Ioana Puscalau-Girtu (I)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Alexander Biedermann (A)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany.

Marcus Fändrich (M)

Institute of Protein Biochemistry, Ulm University, Ulm, Germany. marcus.faendrich@uni-ulm.de.

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Classifications MeSH