title: The circularization of amyloid fibrils formed by apolipoprotein C-II.
abstract: Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a "cross-beta" x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common beta-sheet core structure, they display a substantial degree of morphological variation. One striking example is the remarkable ability of human apolipoprotein C-II amyloid fibrils to circularize and form closed rings. Here we explore in detail the structure of apoC-II amyloid fibrils using electron microscopy, atomic force microscopy, and x-ray diffraction studies. Our results suggest a model for apoC-II fibrils as ribbons approximately 2.1-nm thick and 13-nm wide with a helical repeat distance of 53 nm +/- 12 nm. We propose that the ribbons are highly flexible with a persistence length of 36 nm. We use these observed biophysical properties to model the apoC-II amyloid fibrils either as wormlike chains or using a random-walk approach, and confirm that the probability of ring formation is critically dependent on the fibril flexibility. More generally, the ability of apoC-II fibrils to form rings also highlights the degree to which the common cross-beta superstructure can, as a function of the protein constituent, give rise to great variation in the physical properties of amyloid fibrils.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia.
authors.forename: Danny M
authors.initials: DM
authors.lastname: Hatters
authors.forename: Christopher A
authors.initials: CA
authors.lastname: MacRaild
authors.forename: Rob
authors.initials: R
authors.lastname: Daniels
authors.forename: Walraj S
authors.initials: WS
authors.lastname: Gosal
authors.forename: Neil H
authors.initials: NH
authors.lastname: Thomson
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Jones
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Davis
authors.forename: Cait E
authors.initials: CE
authors.lastname: MacPhee
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C