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 language | English |
|---|---|
| Pages (from-to) | 1033-1039 |
| Number of pages | 7 |
| Journal | Journal of Molecular Biology |
| Volume | 300 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jul 28 2000 |
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Keywords
- Amyloid
- Electron microscopy
- Fibrils
- Image analysis
- Protofilaments
ASJC Scopus subject areas
- Virology
Cite this
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 journal › Article
}
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
C2 - 10903851
AN - SCOPUS:0034725535
VL - 300
SP - 1033
EP - 1039
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 5
ER -