The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II

Danny M. Hatters, Christopher A. MacRaild, Rob Daniels, Walraj S. Gosal, Neil H. Thomson, Jonathan A. Jones, Jason J. Davis, Cait E. MacPhee, Christopher M. Dobson, Geoffrey J. Howlett

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a "cross-β" x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common β-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-β 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 - 1 Jan 2003
Externally publishedYes

Cite this

Hatters, D. M., MacRaild, C. A., Daniels, R., Gosal, W. S., Thomson, N. H., Jones, J. A., ... Howlett, G. J. (2003). The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II. Biophysical Journal, 85(6), 3979-3990. https://doi.org/10.1016/S0006-3495(03)74812-7
Hatters, Danny M. ; MacRaild, Christopher A. ; Daniels, Rob ; Gosal, Walraj S. ; Thomson, Neil H. ; Jones, Jonathan A. ; Davis, Jason J. ; MacPhee, Cait E. ; Dobson, Christopher M. ; Howlett, Geoffrey J. / The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II. In: Biophysical Journal. 2003 ; Vol. 85, No. 6. pp. 3979-3990.
@article{602f2ed90da444cf905af1673b7e0f39,
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-β{"} x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common β-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-β superstructure can, as a function of the protein constituent, give rise to great variation in the physical properties of amyloid fibrils.",
author = "Hatters, {Danny M.} and MacRaild, {Christopher A.} and Rob Daniels and Gosal, {Walraj S.} and Thomson, {Neil H.} and Jones, {Jonathan A.} and Davis, {Jason J.} and MacPhee, {Cait E.} and Dobson, {Christopher M.} and Howlett, {Geoffrey J.}",
year = "2003",
month = "1",
day = "1",
doi = "10.1016/S0006-3495(03)74812-7",
language = "English",
volume = "85",
pages = "3979--3990",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "6",

}

Hatters, DM, MacRaild, CA, Daniels, R, Gosal, WS, Thomson, NH, Jones, JA, Davis, JJ, MacPhee, CE, Dobson, CM & Howlett, GJ 2003, 'The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II' Biophysical Journal, vol. 85, no. 6, pp. 3979-3990. https://doi.org/10.1016/S0006-3495(03)74812-7

The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II. / Hatters, Danny M.; MacRaild, Christopher A.; Daniels, Rob; Gosal, Walraj S.; Thomson, Neil H.; Jones, Jonathan A.; Davis, Jason J.; MacPhee, Cait E.; Dobson, Christopher M.; Howlett, Geoffrey J.

In: Biophysical Journal, Vol. 85, No. 6, 01.01.2003, p. 3979-3990.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II

AU - Hatters, Danny M.

AU - MacRaild, Christopher A.

AU - Daniels, Rob

AU - Gosal, Walraj S.

AU - Thomson, Neil H.

AU - Jones, Jonathan A.

AU - Davis, Jason J.

AU - MacPhee, Cait E.

AU - Dobson, Christopher M.

AU - Howlett, Geoffrey J.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a "cross-β" x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common β-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-β superstructure can, as a function of the protein constituent, give rise to great variation in the physical properties of amyloid fibrils.

AB - Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a "cross-β" x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common β-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-β superstructure can, as a function of the protein constituent, give rise to great variation in the physical properties of amyloid fibrils.

UR - http://www.scopus.com/inward/record.url?scp=10744229371&partnerID=8YFLogxK

U2 - 10.1016/S0006-3495(03)74812-7

DO - 10.1016/S0006-3495(03)74812-7

M3 - Article

VL - 85

SP - 3979

EP - 3990

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 6

ER -