The circularization of amyloid fibrils formed by apolipoprotein C-II.
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.
Hatters
Danny M
DM
Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia.
MacRaild
Christopher A
CA
Daniels
Rob
R
Gosal
Walraj S
WS
Thomson
Neil H
NH
Jones
Jonathan A
JA
Davis
Jason J
JJ
MacPhee
Cait E
CE
Dobson
Christopher M
CM
Howlett
Geoffrey J
GJ
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
D000682:Amyloid; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C