The protofilament substructure of amyloid fibrils

Louise C. Serpell, Margaret Sunde, Merrill Benson, Glenys A. Tennent, Mark B. Pepys, Paul E. Fraser

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes the usually fatal, acquired and hereditary systemic amyloidoses and is associated with the pathology of Alzheimer's disease, type 2 diabetes and the transmissible spongiform encephalopathies. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. We have previously demonstrated that transthyretin amyloid fibrils contain four constituent protofilaments packed in a square array. Here, we have used cross-correlation techniques to average electron microscopy images of multiple cross-sections in order to reconstruct the substructure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal immunoglobulin λ light chain, Leu60Arg variant apolipoprotein AI, and Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten-residue peptide corresponding to the A-strand of transthyretin. All the fibrils had an electron-lucent core but the packing arrangement comprised five or six protofilaments rather than four. The structural similarity that defines amyloid fibres thus exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)1033-1039
Number of pages7
JournalJournal of Molecular Biology
Volume300
Issue number5
DOIs
StatePublished - Jul 28 2000

Fingerprint

Amyloid
Prealbumin
Familial Amyloidosis
Immunoglobulin Light Chains
Amyloidogenic Proteins
Serum Amyloid A Protein
Peptides
Prion Diseases
Apolipoprotein A-I
Amyloidosis
Muramidase
Type 2 Diabetes Mellitus
Electron Microscopy
Electrons
Pathology
Proteins

Keywords

  • Amyloid
  • Electron microscopy
  • Fibrils
  • Image analysis
  • Protofilaments

ASJC Scopus subject areas

  • Virology

Cite this

Serpell, L. C., Sunde, M., Benson, M., Tennent, G. A., Pepys, M. B., & Fraser, P. E. (2000). The protofilament substructure of amyloid fibrils. Journal of Molecular Biology, 300(5), 1033-1039. https://doi.org/10.1006/jmbi.2000.3908

The protofilament substructure of amyloid fibrils. / Serpell, Louise C.; Sunde, Margaret; Benson, Merrill; Tennent, Glenys A.; Pepys, Mark B.; Fraser, Paul E.

In: Journal of Molecular Biology, Vol. 300, No. 5, 28.07.2000, p. 1033-1039.

Research output: Contribution to journalArticle

Serpell, LC, Sunde, M, Benson, M, Tennent, GA, Pepys, MB & Fraser, PE 2000, 'The protofilament substructure of amyloid fibrils', Journal of Molecular Biology, vol. 300, no. 5, pp. 1033-1039. https://doi.org/10.1006/jmbi.2000.3908
Serpell LC, Sunde M, Benson M, Tennent GA, Pepys MB, Fraser PE. The protofilament substructure of amyloid fibrils. Journal of Molecular Biology. 2000 Jul 28;300(5):1033-1039. https://doi.org/10.1006/jmbi.2000.3908
Serpell, Louise C. ; Sunde, Margaret ; Benson, Merrill ; Tennent, Glenys A. ; Pepys, Mark B. ; Fraser, Paul E. / The protofilament substructure of amyloid fibrils. In: Journal of Molecular Biology. 2000 ; Vol. 300, No. 5. pp. 1033-1039.
@article{84763f1ac7a84a4e9d7437779fdae87b,
title = "The protofilament substructure of amyloid fibrils",
abstract = "Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes the usually fatal, acquired and hereditary systemic amyloidoses and is associated with the pathology of Alzheimer's disease, type 2 diabetes and the transmissible spongiform encephalopathies. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. We have previously demonstrated that transthyretin amyloid fibrils contain four constituent protofilaments packed in a square array. Here, we have used cross-correlation techniques to average electron microscopy images of multiple cross-sections in order to reconstruct the substructure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal immunoglobulin λ light chain, Leu60Arg variant apolipoprotein AI, and Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten-residue peptide corresponding to the A-strand of transthyretin. All the fibrils had an electron-lucent core but the packing arrangement comprised five or six protofilaments rather than four. The structural similarity that defines amyloid fibres thus exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments. (C) 2000 Academic Press.",
keywords = "Amyloid, Electron microscopy, Fibrils, Image analysis, Protofilaments",
author = "Serpell, {Louise C.} and Margaret Sunde and Merrill Benson and Tennent, {Glenys A.} and Pepys, {Mark B.} and Fraser, {Paul E.}",
year = "2000",
month = "7",
day = "28",
doi = "10.1006/jmbi.2000.3908",
language = "English",
volume = "300",
pages = "1033--1039",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - The protofilament substructure of amyloid fibrils

AU - Serpell, Louise C.

AU - Sunde, Margaret

AU - Benson, Merrill

AU - Tennent, Glenys A.

AU - Pepys, Mark B.

AU - Fraser, Paul E.

PY - 2000/7/28

Y1 - 2000/7/28

N2 - Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes the usually fatal, acquired and hereditary systemic amyloidoses and is associated with the pathology of Alzheimer's disease, type 2 diabetes and the transmissible spongiform encephalopathies. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. We have previously demonstrated that transthyretin amyloid fibrils contain four constituent protofilaments packed in a square array. Here, we have used cross-correlation techniques to average electron microscopy images of multiple cross-sections in order to reconstruct the substructure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal immunoglobulin λ light chain, Leu60Arg variant apolipoprotein AI, and Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten-residue peptide corresponding to the A-strand of transthyretin. All the fibrils had an electron-lucent core but the packing arrangement comprised five or six protofilaments rather than four. The structural similarity that defines amyloid fibres thus exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments. (C) 2000 Academic Press.

AB - Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes the usually fatal, acquired and hereditary systemic amyloidoses and is associated with the pathology of Alzheimer's disease, type 2 diabetes and the transmissible spongiform encephalopathies. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. We have previously demonstrated that transthyretin amyloid fibrils contain four constituent protofilaments packed in a square array. Here, we have used cross-correlation techniques to average electron microscopy images of multiple cross-sections in order to reconstruct the substructure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal immunoglobulin λ light chain, Leu60Arg variant apolipoprotein AI, and Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten-residue peptide corresponding to the A-strand of transthyretin. All the fibrils had an electron-lucent core but the packing arrangement comprised five or six protofilaments rather than four. The structural similarity that defines amyloid fibres thus exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments. (C) 2000 Academic Press.

KW - Amyloid

KW - Electron microscopy

KW - Fibrils

KW - Image analysis

KW - Protofilaments

UR - http://www.scopus.com/inward/record.url?scp=0034725535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034725535&partnerID=8YFLogxK

U2 - 10.1006/jmbi.2000.3908

DO - 10.1006/jmbi.2000.3908

M3 - Article

VL - 300

SP - 1033

EP - 1039

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 5

ER -