The circularization of amyloid fibrils formed by apolipoprotein C-II

D M Hatters, C A MacRaild, R Daniels, W S Gosal, N H Thomson, J A Jones, J J Davis, C E MacPhee, C M Dobson, G J Howlett, Cait MacPhee

Research output: Contribution to journalArticlepeer-review

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; 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.

Original languageEnglish
Pages (from-to)3979-3990
Number of pages12
JournalBiophysical Journal
Volume85
Issue number6
DOIs
Publication statusPublished - Dec 2003

Keywords

  • MONTE-CARLO SIMULATION
  • GLOBULAR PROTEIN
  • FORCE MICROSCOPY
  • ALPHA-SYNUCLEIN
  • KINETIC-MODEL
  • BETA-PROTEIN
  • FIBRILLIZATION
  • DISEASES

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