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TitleAA amyloid fibrils from diseased tissue are structurally different from in vitro formed SAA fibrils.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 1013, Year 2021
Publish dateFeb 12, 2021
AuthorsAkanksha Bansal / Matthias Schmidt / Matthies Rennegarbe / Christian Haupt / Falk Liberta / Sabrina Stecher / Ioana Puscalau-Girtu / Alexander Biedermann / Marcus Fändrich /
PubMed AbstractSystemic 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 ...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.
External linksNat Commun / PubMed:33579941 / PubMed Central
MethodsEM (helical sym.)
Resolution2.73 - 3.5 Å
Structure data

11162

6zcf

EMDB-11162: amyloid fibril morphology i (in vitro) from murine SAA1 protein
PDB-6zcf: Amyloid fibril morphology i (in vitro) from murine SAA1.1 protein
Method: EM (helical sym.) / Resolution: 2.73 Å

11163

6zcg

EMDB-11163, PDB-6zcg:
Amyloid fibril morphology ii (in vitro) from murine SAA1.1 protein
Method: EM (helical sym.) / Resolution: 2.95 Å

11164

6zch

EMDB-11164, PDB-6zch:
Amyloid fibril morphology II (ex vivo) from murine SAA1.1 protein.
Method: EM (helical sym.) / Resolution: 3.5 Å

Source
  • mus musculus (house mouse)
KeywordsPROTEIN FIBRIL / systemic amyloidosis / misfolding disease / inflammation / prion

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