title: Electron tomography reveals the fibril structure and lipid interactions in amyloid deposits.
abstract: Electron tomography is an increasingly powerful method to study the detailed architecture of macromolecular complexes or cellular structures. Applied to amyloid deposits formed in a cell culture model of systemic amyloid A amyloidosis, we could determine the structural morphology of the fibrils directly in the deposit. The deposited fibrils are arranged in different networks, and depending on the relative fibril orientation, we can distinguish between fibril meshworks, fibril bundles, and amyloid stars. These networks are frequently infiltrated by vesicular lipid inclusions that may originate from the death of the amyloid-forming cells. Our data support the role of nonfibril components for constructing fibril deposits and provide structural views of different types of lipid-fibril interactions.
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Marius
authors.initials: M
authors.lastname: Kollmer
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Katrin
authors.initials: K
authors.lastname: Meinhardt
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Haupt
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Falk
authors.initials: F
authors.lastname: Liberta
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Melanie
authors.initials: M
authors.lastname: Wulff
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Julia
authors.initials: J
authors.lastname: Linder
authors.affiliation: Institute of Stochastics, Ulm University, 89081 Ulm, Germany;
authors.forename: Lisa
authors.initials: L
authors.lastname: Handl
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, 07745 Jena, Germany;
authors.forename: Liesa
authors.initials: L
authors.lastname: Heinrich
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Cornelia
authors.initials: C
authors.lastname: Loos
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, 89081 Ulm, Germany;
authors.forename: Tatiana
authors.initials: T
authors.lastname: Syrovets
authors.affiliation: Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, 89081 Ulm, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.affiliation: Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala SE-751 85, Sweden;
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.affiliation: Department of Medical Cell Biology, Uppsala University, SE-75123 Uppsala, Sweden;
authors.forename: Gunilla T
authors.initials: GT
authors.lastname: Westermark
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, 07745 Jena, Germany;
authors.forename: Uwe
authors.initials: U
authors.lastname: Horn
authors.affiliation: Institute of Stochastics, Ulm University, 89081 Ulm, Germany;
authors.forename: Volker
authors.initials: V
authors.lastname: Schmidt
authors.affiliation: Central Electron Microscopy Facility, Ulm University, 89081 Ulm, Germany paul.walther@uni-ulm.de marcus.faendrich@uni-ulm.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Walther
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany; paul.walther@uni-ulm.de marcus.faendrich@uni-ulm.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D055032:Electron Microscope Tomography / Q000379:methods*; D005260:Female; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D000685:Serum Amyloid A Protein / Q000737:chemistry
chemical_list: D000682:Amyloid; D008051:Lipid Bilayers; D008055:Lipids; C521404:SAA1 protein, human; D000685:Serum Amyloid A Protein
keywords: aggregation; conformational disease; electron tomography; prion; protein assembly