The circularization of amyloid fibrils formed by apolipoprotein C-II.

Journal article

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: Hatters, D; MacRaild, C; Daniels, R; Gosal, W; Thomson, N

• Publication status: Published
• Journal: Biophysical journal
• Volume: 85
• Issue: 6
• Pages: 3979-3990
• Publication date: 2003-12-01
• DOI: 10.1016/s0006-3495(03)74812-7
• EISSN: 1542-0086
• ISSN: 0006-3495
• Language: English
• Keywords: Kinetics; Biophysical Phenomena; Apolipoproteins C; X-Ray Diffraction; Humans; Protein Structure, Secondary; Protein Binding; Biophysics; Amyloid; Apolipoprotein C-II; Monte Carlo Method; Microscopy, Electron; Protein Conformation; Microscopy, Atomic Force